The Role of Mitochondrial Metabolism, AMPK-SIRT Mediated Pathway, LncRNA and MicroRNA in Osteoarthritis

Osteoarthritis (OA) is the most common joint disease characterized by degeneration of articular cartilage and causes severe joint pain, physical disability, and impaired quality of life. Recently, it was found that mitochondria not only act as a powerhouse of cells that provide energy for cellular metabolism, but are also involved in crucial pathways responsible for maintaining chondrocyte physiology. Therefore, a growing amount of evidence emphasizes that impairment of mitochondrial function is associated with OA pathogenesis; however, the exact mechanism is not well known. Moreover, the AMP-activated protein kinase (AMPK)–Sirtuin (SIRT) signaling pathway, long non-coding RNA (lncRNA), and microRNA (miRNA) are important for regulating the physiological and pathological processes of chondrocytes, indicating that these may be targets for OA treatment. In this review, we first focus on the importance of mitochondria metabolic dysregulation related to OA. Then, we show recent evidence on the AMPK-SIRT mediated pathway associated with OA pathogenesis and potential treatment options. Finally, we discuss current research into the effects of lncRNA and miRNA on OA progression or inhibition.

[1]  Yi-Fu Xu,et al.  The protective effects of etomidate against interleukin-1β (IL-1β)-induced oxidative stress, extracellular matrix alteration and cellular senescence in chondrocytes , 2021, Bioengineered.

[2]  Q. Zuo,et al.  Trelagliptin ameliorates IL-1β-impaired chondrocyte function via the AMPK/SOX-9 pathway. , 2021, Molecular immunology.

[3]  Huan Liu,et al.  Mechanisms linking mitochondrial mechanotransduction and chondrocyte biology in the pathogenesis of osteoarthritis , 2021, Ageing Research Reviews.

[4]  Lei Guo,et al.  17β-Estradiol Induces Mitophagy Upregulation to Protect Chondrocytes via the SIRT1-Mediated AMPK/mTOR Signaling Pathway , 2021, Frontiers in Endocrinology.

[5]  Cheng-Chang Lu,et al.  Intra-Articular Injection of (-)-Epigallocatechin 3-Gallate to Attenuate Articular Cartilage Degeneration by Enhancing Autophagy in a Post-Traumatic Osteoarthritis Rat Model , 2020, Antioxidants.

[6]  Hang Lin,et al.  Role of mitochondria in mediating chondrocyte response to mechanical stimuli. , 2020, Life sciences.

[7]  Kang Xu,et al.  Safflower yellow alleviates osteoarthritis and prevents inflammation by inhibiting PGE2 release and regulating NF-κB/SIRT1/AMPK signaling pathways. , 2020, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[8]  Kai Xu,et al.  The role of SIRT3-mediated mitochondrial homeostasis in osteoarthritis , 2020, Cellular and Molecular Life Sciences.

[9]  Simon W. Jones,et al.  Regulation of the Inflammatory Synovial Fibroblast Phenotype by Metastasis‐Associated Lung Adenocarcinoma Transcript 1 Long Noncoding RNA in Obese Patients With Osteoarthritis , 2020, Arthritis & rheumatology.

[10]  M. M. Schilling,et al.  Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha , 2020, Definitions.

[11]  W. Liao,et al.  Mitochondrial DNA haplogroups participate in osteoarthritis: current evidence based on a meta-analysis , 2020, Clinical Rheumatology.

[12]  T. Griffin,et al.  Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis , 2020, Connective tissue research.

[13]  L. Bonassar,et al.  Mitoprotective therapy prevents rapid, strain‐dependent mitochondrial dysfunction after articular cartilage injury , 2019, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[14]  Hong Wei,et al.  Exendin-4 Protects against Hyperglycemia-Induced Cardiomyocyte Pyroptosis via the AMPK-TXNIP Pathway , 2019, Journal of diabetes research.

[15]  Yao Li,et al.  Mangiferin Prevents TBHP-Induced Apoptosis and ECM Degradation in Mouse Osteoarthritic Chondrocytes via Restoring Autophagy and Ameliorates Murine Osteoarthritis , 2019, Oxidative medicine and cellular longevity.

[16]  I. Clark,et al.  The function of microRNAs in cartilage and osteoarthritis. , 2019, Clinical and experimental rheumatology.

[17]  Rui Wang,et al.  Effect of chondrocyte mitochondrial dysfunction on cartilage degeneration: A possible pathway for osteoarthritis pathology at the subcellular level , 2019, Molecular medicine reports.

[18]  Shi-jie Han,et al.  Chondroitin sulfate from sturgeon bone protects chondrocytes via inhibiting apoptosis in osteoarthritis. , 2019, International journal of biological macromolecules.

[19]  T. Karlsen,et al.  Multi-pathway Protective Effects of MicroRNAs on Human Chondrocytes in an In Vitro Model of Osteoarthritis , 2019, Molecular therapy. Nucleic acids.

[20]  Liu Yang,et al.  LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis , 2019, Cell & Bioscience.

[21]  M. J. López-Armada,et al.  Role of mitochondrial dysfunction on rheumatic diseases. , 2019, Biochemical pharmacology.

[22]  Kang Chen,et al.  LncRNA MEG3 Inhibits the Degradation of the Extracellular Matrix of Chondrocytes in Osteoarthritis via Targeting miR-93/TGFBR2 Axis , 2019, Cartilage.

[23]  Mingwei Jiang,et al.  LncRNA PACER is down-regulated in osteoarthritis and regulates chondrocyte apoptosis and lncRNA HOTAIR expression , 2019, Bioscience reports.

[24]  Yang Wang,et al.  Cellular functions of long noncoding RNAs , 2019, Nature Cell Biology.

[25]  Shuogui Xu,et al.  LncRNA FOXD2-AS1 induces chondrocyte proliferation through sponging miR-27a-3p in osteoarthritis , 2019, Artificial cells, nanomedicine, and biotechnology.

[26]  D. Cai,et al.  MiR-146b accelerates osteoarthritis progression by targeting alpha-2-macroglobulin , 2019, Aging.

[27]  Yonggen Zou,et al.  Knockdown of LncRNA H19 Relieves LPS-Induced Damage by Modulating miR-130a in Osteoarthritis , 2019, Yonsei medical journal.

[28]  A. Papavassiliou,et al.  Redox and NF‐&kgr;B signaling in osteoarthritis , 2019, Free radical biology & medicine.

[29]  R. Loeser,et al.  Reactive oxygen species, aging and articular cartilage homeostasis , 2019, Free radical biology & medicine.

[30]  Hong Sun,et al.  Emerging roles of long noncoding RNA in chondrogenesis, osteogenesis, and osteoarthritis. , 2019, American journal of translational research.

[31]  Yueqi Zhang,et al.  Protective effects of metformin against osteoarthritis through upregulation of SIRT3-mediated PINK1/Parkin-dependent mitophagy in primary chondrocytes. , 2018, Bioscience trends.

[32]  O. Akinloye,et al.  First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid , 2018, Alexandria Journal of Medicine.

[33]  R. Terkeltaub,et al.  Activation of AMPK-SIRT3 signaling is chondroprotective by preserving mitochondrial DNA integrity and function. , 2018, Osteoarthritis and cartilage.

[34]  R. Loeser,et al.  Does Joint Injury Make Young Joints Old? , 2018, The Journal of the American Academy of Orthopaedic Surgeons.

[35]  Xiaolei Zhang,et al.  SIRT3 Activation by Dihydromyricetin Suppresses Chondrocytes Degeneration via Maintaining Mitochondrial Homeostasis , 2018, International journal of biological sciences.

[36]  Qiugeng Wang,et al.  LncRNA FOXD2-AS1 regulates chondrocyte proliferation in osteoarthritis by acting as a sponge of miR-206 to modulate CCND1 expression. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[37]  B. Lardy,et al.  Reactive oxygen species and NADPH oxidase 4 involvement in osteoarthritis , 2018, Experimental Gerontology.

[38]  Wei Zhang,et al.  Lower range of molecular weight of xanthan gum inhibits cartilage matrix destruction via intrinsic bax-mitochondria cytochrome c-caspase pathway. , 2018, Carbohydrate polymers.

[39]  T. Haqqi,et al.  Butein Activates Autophagy Through AMPK/TSC2/ULK1/mTOR Pathway to Inhibit IL-6 Expression in IL-1β Stimulated Human Chondrocytes , 2018, Cellular Physiology and Biochemistry.

[40]  C. Malemud MicroRNAs and Osteoarthritis , 2018, Cells.

[41]  I. Rego-Pérez,et al.  Mitochondria and mitophagy: biosensors for cartilage degradation and osteoarthritis. , 2018, Osteoarthritis and cartilage.

[42]  E. Tchetina,et al.  Regulation of energy metabolism in the growth plate and osteoarthritic chondrocytes , 2018, Rheumatology International.

[43]  B. Mumey,et al.  Physiological dynamic compression regulates central energy metabolism in primary human chondrocytes , 2018, Biomechanics and Modeling in Mechanobiology.

[44]  Li-Nan Qiu,et al.  Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[45]  Zubin Zhou,et al.  Puerarin Attenuates Osteoarthritis via Upregulating AMP-Activated Protein Kinase/Proliferator-Activated Receptor-γ Coactivator-1 Signaling Pathway in Osteoarthritis Rats , 2018, Pharmacology.

[46]  L. Jia,et al.  Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/β-catenin axis , 2018, Cell Death & Disease.

[47]  Yue Zhang,et al.  LncRNA MALAT1 negatively regulates MDSCs in patients with lung cancer , 2018, Journal of Cancer.

[48]  A. Valdes,et al.  Mitochondrial DNA variation and the pathogenesis of osteoarthritis phenotypes , 2018, Nature Reviews Rheumatology.

[49]  A. Sugimoto,et al.  Apple procyanidins promote mitochondrial biogenesis and proteoglycan biosynthesis in chondrocytes , 2018, Scientific Reports.

[50]  Z-X Wei,et al.  LncRNA FAS-AS1 promotes the degradation of extracellular matrix of cartilage in osteoarthritis. , 2018, European review for medical and pharmacological sciences.

[51]  Guan-qing Wu,et al.  Attenuation of TGFBR2 expression and tumour progression in prostate cancer involve diverse hypoxia-regulated pathways , 2018, Journal of Experimental & Clinical Cancer Research.

[52]  T. Jia,et al.  Long noncoding RNA maternally expressed gene 3 knockdown alleviates lipopolysaccharide-induced inflammatory injury by up-regulation of miR-203 in ATDC5 cells. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[53]  R. Ranka,et al.  Mitochondria, its DNA and telomeres in ageing and human population , 2018, Biogerontology.

[54]  Liyun Wang,et al.  Calcium signaling of in situ chondrocytes in articular cartilage under compressive loading: Roles of calcium sources and cell membrane ion channels , 2018, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[55]  S. Lipton,et al.  Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 , 2018, Cell Death & Differentiation.

[56]  R. Shaw,et al.  AMPK: guardian of metabolism and mitochondrial homeostasis , 2017, Nature Reviews Molecular Cell Biology.

[57]  Chuandong Wang,et al.  MicroRNA-145 attenuates TNF-α-driven cartilage matrix degradation in osteoarthritis via direct suppression of MKK4 , 2017, Cell Death and Disease.

[58]  J. Saucerman,et al.  Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy , 2017, Nature Communications.

[59]  I. Ahmad,et al.  Parkin clearance of dysfunctional mitochondria regulates ROS levels and increases survival of human chondrocytes. , 2017, Osteoarthritis and cartilage.

[60]  Milen I Georgiev,et al.  Oxidative stress and chronic inflammation in osteoarthritis: can NRF2 counteract these partners in crime? , 2017, Annals of the New York Academy of Sciences.

[61]  Yingmei Zhang,et al.  Sirt3 deficiency exacerbates diabetic cardiac dysfunction: Role of Foxo3A-Parkin-mediated mitophagy. , 2017, Biochimica et biophysica acta. Molecular basis of disease.

[62]  S. Sollott,et al.  Mitochondrial membrane potential. , 2017, Analytical biochemistry.

[63]  T. Kamarul,et al.  Evaluating the Protective Effects and Mechanisms of Diallyl Disulfide on Interlukin‐1β‐Induced Oxidative Stress and Mitochondrial Apoptotic Signaling Pathways in Cultured Chondrocytes , 2017, Journal of cellular biochemistry.

[64]  Yimin Yan,et al.  Underlying mechanism of Sirt1 on apoptosis and extracellular matrix degradation of osteoarthritis chondrocytes. , 2017, Molecular medicine reports.

[65]  R. Shaw,et al.  AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance. , 2017, Molecular cell.

[66]  J. Elisseeff,et al.  Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment , 2017, Nature Medicine.

[67]  M. Soriano,et al.  Who and how in the regulation of mitochondrial cristae shape and function. , 2017, Biochemical and biophysical research communications.

[68]  L. Qin,et al.  miR-181a Modulates Chondrocyte Apoptosis by Targeting Glycerol-3-Phosphate Dehydrogenase 1-Like Protein (GPD1L) in Osteoarthritis , 2017, Medical science monitor : international medical journal of experimental and clinical research.

[69]  Yu-sheng Li,et al.  Cellular aging towards osteoarthritis , 2017, Mechanisms of Ageing and Development.

[70]  X. Bai,et al.  Intra-articular Delivery of Antago-miR-483-5p Inhibits Osteoarthritis by Modulating Matrilin 3 and Tissue Inhibitor of Metalloproteinase 2. , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[71]  S. Pértega,et al.  A replication study and meta-analysis of mitochondrial DNA variants in the radiographic progression of knee osteoarthritis , 2017, Rheumatology.

[72]  Weihong Zhu,et al.  Long non-coding RNA HOTAIR promotes expression of ADAMTS-5 in human osteoarthritic articular chondrocytes. , 2017, Die Pharmazie.

[73]  Yuki Tochigi,et al.  Time‐dependent loss of mitochondrial function precedes progressive histologic cartilage degeneration in a rabbit meniscal destabilization model , 2017, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[74]  T. S. Rai,et al.  Cellular senescence in osteoarthritis pathology , 2017, Aging cell.

[75]  Di Chen,et al.  Osteoarthritis: toward a comprehensive understanding of pathological mechanism , 2017, Bone Research.

[76]  S. Pértega,et al.  Mitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts. A meta-analysis and functional study , 2016, Annals of the rheumatic diseases.

[77]  Feng Zhang,et al.  Prophylaxis of Diallyl Disulfide on Skin Carcinogenic Model via p21-dependent Nrf2 stabilization , 2016, Scientific Reports.

[78]  M. Lazarou,et al.  Deciphering the Molecular Signals of PINK1/Parkin Mitophagy. , 2016, Trends in cell biology.

[79]  Md. Shahedur Rahman,et al.  Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease , 2016, Aging cell.

[80]  V. Lowe,et al.  Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[81]  C. Helmick,et al.  Updated Projected Prevalence of Self‐Reported Doctor‐Diagnosed Arthritis and Arthritis‐Attributable Activity Limitation Among US Adults, 2015–2040 , 2016, Arthritis & rheumatology.

[82]  D. Rubinsztein,et al.  Mammalian Autophagy: How Does It Work? , 2016, Annual review of biochemistry.

[83]  K. Staines,et al.  New developments in osteoarthritis and cartilage biology. , 2016, Current opinion in pharmacology.

[84]  A. Papavassiliou,et al.  ROS/oxidative stress signaling in osteoarthritis. , 2016, Biochimica et biophysica acta.

[85]  J. Auwerx,et al.  Mitonuclear communication in homeostasis and stress , 2016, Nature Reviews Molecular Cell Biology.

[86]  P. Ramakrishnan,et al.  Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function , 2016, Arthritis & rheumatology.

[87]  Hua Guo,et al.  PFKFB3 modulates glycolytic metabolism and alleviates endoplasmic reticulum stress in human osteoarthritis cartilage , 2016, Clinical and experimental pharmacology & physiology.

[88]  Guang-xian Li,et al.  Overexpression of microRNA-210 promotes chondrocyte proliferation and extracellular matrix deposition by targeting HIF-3α in osteoarthritis. , 2016, Molecular medicine reports.

[89]  Mark Ellisman,et al.  NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria , 2016, Cell.

[90]  M. Velarde,et al.  Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype. , 2016, Cell metabolism.

[91]  J. Hilmer,et al.  Mechanotransduction in primary human osteoarthritic chondrocytes is mediated by metabolism of energy, lipids, and amino acids. , 2015, Journal of biomechanics.

[92]  Xianzhe Liu,et al.  MicroRNA-16-5p Controls Development of Osteoarthritis by Targeting SMAD3 in Chondrocytes. , 2015, Current pharmaceutical design.

[93]  M. Cohen-Solal,et al.  Subchondral bone and osteoarthritis , 2015, Current opinion in rheumatology.

[94]  T. Sasho,et al.  Mechanical overloading causes mitochondrial superoxide and SOD2 imbalance in chondrocytes resulting in cartilage degeneration , 2015, Scientific Reports.

[95]  M. Lotz,et al.  The Relationship of Autophagy Defects to Cartilage Damage During Joint Aging in a Mouse Model , 2015, Arthritis & rheumatology.

[96]  Wen Xie,et al.  The Long Noncoding RNA MEG3 Is Downregulated and Inversely Associated with VEGF Levels in Osteoarthritis , 2015, BioMed research international.

[97]  R. Terkeltaub,et al.  Mitochondrial Biogenesis Is Impaired in Osteoarthritis Chondrocytes but Reversible via Peroxisome Proliferator–Activated Receptor γ Coactivator 1α , 2015, Arthritis & rheumatology.

[98]  N. Oreiro,et al.  Mitochondrial DNA haplogroups modulate the radiographic progression of Spanish patients with osteoarthritis , 2015, Rheumatology International.

[99]  J. Song,et al.  A long non‐coding RNA, GAS5, plays a critical role in the regulation of miR‐21 during osteoarthritis , 2014, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[100]  Li-Yan Xu,et al.  Identification of Long Noncoding RNA Associated with Osteoarthritis in Humans , 2014, Orthopaedic surgery.

[101]  B. Viollet,et al.  Peroxisome Proliferator–Activated Receptor γ Coactivator 1α and FoxO3A Mediate Chondroprotection by AMP‐Activated Protein Kinase , 2014, Arthritis & rheumatology.

[102]  Brian David Dynlacht,et al.  Foxk proteins repress the initiation of starvation-induced atrophy and autophagy programs , 2014, Nature Cell Biology.

[103]  Di Chen,et al.  Osteoarthritis Pathogenesis: A Review of Molecular Mechanisms , 2014, Calcified Tissue International.

[104]  A. Pearsall,et al.  The role of mitochondrial reactive oxygen species in cartilage matrix destruction , 2014, Molecular and Cellular Biochemistry.

[105]  A. Phaniendra,et al.  Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases , 2014, Indian Journal of Clinical Biochemistry.

[106]  A. Gelber In the clinic. Osteoarthritis. , 2014, Annals of internal medicine.

[107]  Pavel Vodicka,et al.  HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients. , 2014, Carcinogenesis.

[108]  M. Vawter,et al.  Inherited mitochondrial DNA variants can affect complement, inflammation and apoptosis pathways: insights into mitochondrial-nuclear interactions. , 2014, Human molecular genetics.

[109]  M. Lotz,et al.  Autophagy activation protects from mitochondrial dysfunction in human chondrocytes , 2014 .

[110]  Weimin Fan,et al.  Protection of ginsenoside Rg1 on chondrocyte from IL-1β-induced mitochondria-activated apoptosis through PI3K/Akt signaling , 2014, Molecular and Cellular Biochemistry.

[111]  N. Oreiro,et al.  mtDNA haplogroups and osteoarthritis in different geographic populations. , 2014, Mitochondrion.

[112]  L. Guarente,et al.  SIRT1 and other sirtuins in metabolism , 2014, Trends in Endocrinology & Metabolism.

[113]  Rongxin Zhang,et al.  Regulatory non-coding RNAs: revolutionizing the RNA world , 2014, Molecular Biology Reports.

[114]  H. Chi,et al.  Role of mtDNA Haplogroups in the Prevalence of Knee Osteoarthritis in a Southern Chinese Population , 2014, International journal of molecular sciences.

[115]  Xianzhe Liu,et al.  MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes , 2014, Experimental & Molecular Medicine.

[116]  J. Nunnari,et al.  Mitochondrial form and function , 2014, Nature.

[117]  Eric H. Baehrecke,et al.  Self-consumption: the interplay of autophagy and apoptosis , 2014, Nature Reviews Molecular Cell Biology.

[118]  E. Bossy‐Wetzel,et al.  Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration , 2013, Front. Aging Neurosci..

[119]  B. Cillero-Pastor,et al.  Mitochondrial respiratory chain dysfunction modulates metalloproteases -1, -3 and -13 in human normal chondrocytes in culture , 2013, BMC Musculoskeletal Disorders.

[120]  Miyuki Sato,et al.  Maternal inheritance of mitochondrial DNA by diverse mechanisms to eliminate paternal mitochondrial DNA. , 2013, Biochimica et biophysica acta.

[121]  I. Clark,et al.  Review: the role of microRNAs in osteoarthritis and chondrogenesis. , 2013, Arthritis and rheumatism.

[122]  R. Patel,et al.  Interaction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and protects from apoptotic cell death under oxidative stress , 2013, Cell Death and Disease.

[123]  E. Cheon,et al.  MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes. , 2013, Osteoarthritis and cartilage.

[124]  Kelly J. Morris,et al.  A complex secretory program orchestrated by the inflammasome controls paracrine senescence , 2013, Nature Cell Biology.

[125]  George S. B. Williams,et al.  Mitochondrial calcium uptake , 2013, Proceedings of the National Academy of Sciences.

[126]  M. Takigawa,et al.  Impaired glycolytic metabolism causes chondrocyte hypertrophy-like changes via promotion of phospho-Smad1/5/8 translocation into nucleus. , 2013, Osteoarthritis and cartilage.

[127]  Steven P. Gygi,et al.  Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization , 2013, Nature.

[128]  Stephanie Xie,et al.  SIRT3 reverses aging-associated degeneration. , 2013, Cell reports.

[129]  J. Buckwalter,et al.  Mechanical stress and ATP synthesis are coupled by mitochondrial oxidants in articular cartilage , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[130]  D. Hardie,et al.  Metabolism of inflammation limited by AMPK and pseudo-starvation , 2013, Nature.

[131]  Wan-chun Wang,et al.  Reactive Oxygen Species: The 2-Edged Sword of Osteoarthritis , 2012, The American journal of the medical sciences.

[132]  Å. Gustafsson,et al.  Mitochondria and Mitophagy: The Yin and Yang of Cell Death Control , 2012, Circulation research.

[133]  L. Galluzzi,et al.  Mitochondrial Control of Cellular Life, Stress, and Death , 2012, Circulation research.

[134]  Eun-Cheol Kim,et al.  Cytoprotective and anti‐inflammatory effects of melatonin in hydrogen peroxide‐stimulated CHON‐001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway , 2012, Journal of pineal research.

[135]  Jiujiu Yu,et al.  Critical role for calcium mobilization in activation of the NLRP3 inflammasome , 2012, Proceedings of the National Academy of Sciences.

[136]  W. Richter,et al.  Regulation of H19 and its encoded microRNA-675 in osteoarthritis and under anabolic and catabolic in vitro conditions , 2012, Journal of Molecular Medicine.

[137]  Qian Chen,et al.  miR-146a, an IL-1β responsive miRNA, induces vascular endothelial growth factor and chondrocyte apoptosis by targeting Smad4 , 2012, Arthritis Research & Therapy.

[138]  J. Buckwalter,et al.  Cytoskeletal dissolution blocks oxidant release and cell death in injured cartilage , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[139]  A. Salminen,et al.  AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network , 2012, Ageing Research Reviews.

[140]  J. Denu,et al.  SIRT3 Protein Deacetylates Isocitrate Dehydrogenase 2 (IDH2) and Regulates Mitochondrial Redox Status*♦ , 2012, The Journal of Biological Chemistry.

[141]  Jia Xu,et al.  Cross-Talk between AMPK and mTOR in Regulating Energy Balance , 2012, Critical reviews in food science and nutrition.

[142]  Ning Zuo,et al.  Primary cilia mediate mechanotransduction through control of ATP‐induced Ca2+ signaling in compressed chondrocytes , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[143]  J. Auwerx,et al.  Calorie restriction: is AMPK a key sensor and effector? , 2011, Physiology.

[144]  A. Brandl,et al.  Oxidative stress induces senescence in chondrocytes , 2011, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[145]  Simon Tavaré,et al.  Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes , 2011, Science.

[146]  A. Salminen,et al.  AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan , 2011, Journal of Molecular Medicine.

[147]  F. Blanco,et al.  The role of mitochondria in osteoarthritis , 2011, Nature Reviews Rheumatology.

[148]  S. Ryter,et al.  Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. , 2011, Nature immunology.

[149]  L. Scorrano,et al.  During autophagy mitochondria elongate, are spared from degradation and sustain cell viability , 2011, Nature Cell Biology.

[150]  B. Viollet,et al.  AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 , 2011, Nature Cell Biology.

[151]  B. Viollet,et al.  Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy , 2011, Science.

[152]  S. Ryter,et al.  Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release , 2010, Nature Immunology.

[153]  E. Verdin,et al.  Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. , 2010, Trends in biochemical sciences.

[154]  P. Xu,et al.  Mitochondrial function is altered in articular chondrocytes of an endemic osteoarthritis, Kashin-Beck disease. , 2010, Osteoarthritis and cartilage.

[155]  J. Auwerx,et al.  AMP-activated protein kinase and its downstream transcriptional pathways , 2010, Cellular and Molecular Life Sciences.

[156]  M. Lotz,et al.  Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. , 2010, Arthritis and rheumatism.

[157]  I. Ara,et al.  Human mitochondrial haplogroup H: the highest VO2max consumer--is it a paradox? , 2010, Mitochondrion.

[158]  Kanji Fukuda [Progress of research in osteoarthritis. Involvement of reactive oxygen species in the pathogenesis of osteoarthritis]. , 2009, Clinical calcium.

[159]  T. Matsushita,et al.  SIRT1 regulation of apoptosis of human chondrocytes. , 2009, Arthritis and rheumatism.

[160]  P. Puigserver,et al.  AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity , 2009, Nature.

[161]  C. L. Murphy,et al.  The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13. , 2009, Osteoarthritis and cartilage.

[162]  A. Mantovani,et al.  Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals , 2009, Proceedings of the National Academy of Sciences.

[163]  J. Gómez-Reino,et al.  Role of European mitochondrial DNA haplogroups in the prevalence of hip osteoarthritis in Galicia, Northern Spain , 2009, Annals of the rheumatic diseases.

[164]  J. Mateos,et al.  Mitochondrial Dysregulation of Osteoarthritic Human Articular Chondrocytes Analyzed by Proteomics , 2009, Molecular & Cellular Proteomics.

[165]  Michael P. Murphy,et al.  How mitochondria produce reactive oxygen species , 2008, The Biochemical journal.

[166]  Judith Campisi,et al.  Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor , 2008, PLoS biology.

[167]  S. Abramson,et al.  The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production. , 2008, Arthritis and rheumatism.

[168]  I. Shapiro,et al.  Autophagy: A New Phase in the Maturation of Growth Plate Chondrocytes Is Regulated by HIF, mTOR and AMP Kinase , 2008, Cells Tissues Organs.

[169]  J. Arenas,et al.  Mitochondrial DNA haplogroups: role in the prevalence and severity of knee osteoarthritis. , 2008, Arthritis and rheumatism.

[170]  B. Turk,et al.  AMPK phosphorylation of raptor mediates a metabolic checkpoint. , 2008, Molecular cell.

[171]  M. Shakibaei,et al.  Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro. , 2008, Biochemical pharmacology.

[172]  A. Goldberg,et al.  FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. , 2007, Cell metabolism.

[173]  S. Gygi,et al.  The Energy Sensor AMP-activated Protein Kinase Directly Regulates the Mammalian FOXO3 Transcription Factor* , 2007, Journal of Biological Chemistry.

[174]  B. Spiegelman,et al.  AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α , 2007, Proceedings of the National Academy of Sciences.

[175]  M. Davies,et al.  Calcium signaling leads to mitochondrial depolarization in impact-induced chondrocyte death in equine articular cartilage explants. , 2007, Arthritis and rheumatism.

[176]  T. Aigner,et al.  Mechanisms of Disease: role of chondrocytes in the pathogenesis of osteoarthritis—structure, chaos and senescence , 2007, Nature Clinical Practice Rheumatology.

[177]  Karl-Heinz Krause,et al.  Aging: A revisited theory based on free radicals generated by NOX family NADPH oxidases , 2007, Experimental Gerontology.

[178]  F. Blanco,et al.  Cell death and apoptosis in osteoarthritic cartilage. , 2007, Current drug targets.

[179]  Kang-hua Li,et al.  Mitochondrial DNA deletion mutations in articular chondrocytes of cartilage affected by osteoarthritis. , 2006, Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences.

[180]  B. Cillero-Pastor,et al.  Mitochondrial activity is modulated by TNFα and IL-1β in normal human chondrocyte cells , 2006 .

[181]  M. Derouazi,et al.  NAD(P)H oxidase activity of Nox4 in chondrocytes is both inducible and involved in collagenase expression. , 2006, Antioxidants & redox signaling.

[182]  J. Mattick,et al.  Non-coding RNA. , 2006, Human molecular genetics.

[183]  B Kurz,et al.  Oxygen and reactive oxygen species in cartilage degradation: friends or foes? , 2005, Osteoarthritis and cartilage.

[184]  R. Scarpulla,et al.  Control of Mitochondrial Transcription Specificity Factors (TFB1M and TFB2M) by Nuclear Respiratory Factors (NRF-1 and NRF-2) and PGC-1 Family Coactivators , 2005, Molecular and Cellular Biology.

[185]  J. Urban,et al.  Factors influencing the oxygen concentration gradient from the synovial surface of articular cartilage to the cartilage-bone interface: a modeling study. , 2004, Arthritis and rheumatism.

[186]  M. D. de Andrés,et al.  Effect of nitric oxide on mitochondrial respiratory activity of human articular chondrocytes , 2004, Annals of the rheumatic diseases.

[187]  Marty C. Brandon,et al.  Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA , 2004, Science.

[188]  K. Inoki,et al.  TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival , 2003, Cell.

[189]  Y. Henrotin,et al.  The role of reactive oxygen species in homeostasis and degradation of cartilage. , 2003, Osteoarthritis and cartilage.

[190]  M. D. de Andrés,et al.  Mitochondrial respiratory activity is altered in osteoarthritic human articular chondrocytes. , 2003, Arthritis and rheumatism.

[191]  T. Aigner,et al.  Roles of chondrocytes in the pathogenesis of osteoarthritis. , 2002, Current opinion in rheumatology.

[192]  R. Terkeltaub,et al.  Invited review: the mitochondrion in osteoarthritis. , 2002, Mitochondrion.

[193]  A. Grodzinsky,et al.  Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis. , 2000, Archives of biochemistry and biophysics.

[194]  R. Terkeltaub,et al.  Mitochondrial oxidative phosphorylation is a downstream regulator of nitric oxide effects on chondrocyte matrix synthesis and mineralization. , 2000, Arthritis and rheumatism.

[195]  M. Duchen,et al.  Contributions of mitochondria to animal physiology: from homeostatic sensor to calcium signalling and cell death , 1999, The Journal of physiology.

[196]  G. Brown,et al.  Release of cytochrome c from heart mitochondria is induced by high Ca2+ and peroxynitrite and is responsible for Ca(2+)-induced inhibition of substrate oxidation. , 1999, Biochimica et biophysica acta.

[197]  G. Barsh,et al.  Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice , 1998, Nature Genetics.

[198]  J. Hancock,et al.  NADPH oxidase of chondrocytes contains an isoform of the gp91phox subunit. , 1998, The Biochemical journal.

[199]  P. Otte Basic cell metabolism of articular cartilage. Manometric studies. , 1991, Zeitschrift fur Rheumatologie.

[200]  I. Shapiro,et al.  Adenine, guanine, and inosine nucleotides of chick growth cartilage: Relationship between energy status and the mineralization process , 1988, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[201]  B. Chance,et al.  Initiation of endochondral calcification is related to changes in the redox state of hypertrophic chondrocytes. , 1982, Science.

[202]  F. Sanger,et al.  Sequence and organization of the human mitochondrial genome , 1981, Nature.

[203]  Simon W. Jones,et al.  Obese osteoarthritis patients exhibit an inflammatory synovial fibroblast phenotype, which is regulated by the long non coding RNA MALAT1 , 2019 .

[204]  Kee-Lung Chang,et al.  Zinc protects chondrocytes from monosodium iodoacetate-induced damage by enhancing ATP and mitophagy. , 2019, Biochemical and biophysical research communications.

[205]  P. Sacitharan Ageing and Osteoarthritis. , 2019, Sub-cellular biochemistry.

[206]  J. S. Sousa,et al.  Mitochondrial Respiratory Chain Complexes. , 2018, Sub-cellular biochemistry.

[207]  L. Jia,et al.  MiR-26a and miR-26b mediate osteoarthritis progression by targeting FUT4 via NF-κB signaling pathway. , 2018, The international journal of biochemistry & cell biology.

[208]  R. Loeser,et al.  Targeting aging for disease modification in osteoarthritis , 2018, Current opinion in rheumatology.

[209]  Kai Huang,et al.  Non-coding RNAs as regulators in epigenetics (Review). , 2017, Oncology reports.

[210]  C. Malemud Matrix Metalloproteinases and Synovial Joint Pathology. , 2017, Progress in molecular biology and translational science.

[211]  P. Park,et al.  Neuroprotective Effect of Taurine-Rich Cuttlefish (Sepia officinalis) Extract Against Hydrogen Peroxide-Induced Oxidative Stress in SH-SY5Y Cells. , 2017, Advances in experimental medicine and biology.

[212]  R. Terkeltaub,et al.  Emerging regulators of the inflammatory process in osteoarthritis , 2015, Nature Reviews Rheumatology.

[213]  Xiaoling Li SIRT1 and energy metabolism. , 2013, Acta biochimica et biophysica Sinica.

[214]  S. Ryter,et al.  Autophagy in human health and disease. , 2013, The New England journal of medicine.

[215]  Xiaoling Li SIRT 1 and energy metabolism , 2012 .

[216]  K. Mulhall,et al.  Basic and translational research , 2011 .

[217]  高山 孝治 SIRT1 regulation of apoptosis of human chondrocytes , 2011 .

[218]  M. Monsalve,et al.  Mutual dependence of Foxo3a and PGC-1alpha in the induction of oxidative stress genes. , 2009, The Journal of biological chemistry.

[219]  B. Cillero-Pastor,et al.  Mitochondrial activity is modulated by TNFalpha and IL-1beta in normal human chondrocyte cells. , 2006, Osteoarthritis and cartilage.

[220]  A. Calabrese,et al.  Intercellular Ca2+ waves in mechanically stimulated articular chondrocytes. , 2000, Biorheology.

[221]  C. Sen Oxygen toxicity and antioxidants: state of the art. , 1995, Indian journal of physiology and pharmacology.

[222]  R. Ochs,et al.  Chondrocyte apoptosis induced by nitric oxide. , 1995, The American journal of pathology.

[223]  D. Wallace Maternal genes: mitochondrial diseases. , 1987, Birth defects original article series.

[224]  R. E. Marcus The effect of low oxygen concentration on growth, glycolysis, and sulfate incorporation by articular chondrocytes in monolayer culture. , 1973, Arthritis and rheumatism.