The Effect of CaV1.2 Inhibitor Nifedipine on Chondrogenic Differentiation of Human Bone Marrow or Menstrual Blood-Derived Mesenchymal Stem Cells and Chondrocytes

Cartilage is an avascular tissue and sensitive to mechanical trauma and/or age-related degenerative processes leading to the development of osteoarthritis (OA). Therefore, it is important to investigate the mesenchymal cell-based chondrogenic regenerating mechanisms and possible their regulation. The aim of this study was to investigate the role of intracellular calcium (iCa2+) and its regulation through voltage-operated calcium channels (VOCC) on chondrogenic differentiation of mesenchymal stem/stromal cells derived from human bone marrow (BMMSCs) and menstrual blood (MenSCs) in comparison to OA chondrocytes. The level of iCa2+ was highest in chondrocytes, whereas iCa2+ store capacity was biggest in MenSCs and they proliferated better as compared to other cells. The level of CaV1.2 channels was also highest in OA chondrocytes than in other cells. CaV1.2 antagonist nifedipine slightly suppressed iCa2+, Cav1.2 and the proliferation of all cells and affected iCa2+ stores, particularly in BMMSCs. The expression of the CaV1.2 gene during 21 days of chondrogenic differentiation was highest in MenSCs, showing the weakest chondrogenic differentiation, which was stimulated by the nifedipine. The best chondrogenic differentiation potential showed BMMSCs (SOX9 and COL2A1 expression); however, purposeful iCa2+ and VOCC regulation by blockers can stimulate a chondrogenic response at least in MenSCs.

[1]  W. Tsai,et al.  Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair , 2023, International journal of molecular sciences.

[2]  W. Tsai,et al.  The Effects of Mechanical Load on Chondrogenic Responses of Bone Marrow Mesenchymal Stem Cells and Chondrocytes Encapsulated in Chondroitin Sulfate-Based Hydrogel , 2023, International journal of molecular sciences.

[3]  M. Figueiredo-Dias,et al.  The Emerging Role of Menstrual-Blood-Derived Stem Cells in Endometriosis , 2022, Biomedicines.

[4]  Silvia Liu,et al.  Differences in the intrinsic chondrogenic potential of human mesenchymal stromal cells and iPSC‐derived multipotent cells , 2022, Clinical and translational medicine.

[5]  M. Dieterle,et al.  Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies , 2021, Expert Reviews in Molecular Medicine.

[6]  A. Mobasheri,et al.  Cardiovascular Drugs and Osteoarthritis: Effects of Targeting Ion Channels , 2021, Cells.

[7]  A. Mobasheri,et al.  Different phenotypes and chondrogenic responses of human menstrual blood and bone marrow mesenchymal stem cells to activin A and TGF-β3 , 2020, Stem cell research & therapy.

[8]  M. Previati,et al.  Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer , 2020, International journal of molecular sciences.

[9]  P. Pinton,et al.  Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology , 2020, Biomolecules.

[10]  K. Nakayama,et al.  Osteochondral Regeneration Using Adipose Tissue-Derived Mesenchymal Stem Cells , 2020, International journal of molecular sciences.

[11]  Nicholas M. Wragg,et al.  Intraarticular injection of bone marrow-derived mesenchymal stem cells enhances regeneration in knee osteoarthritis , 2020, Knee Surgery, Sports Traumatology, Arthroscopy.

[12]  M. Pichler,et al.  Calcium Signaling in ß-cell Physiology and Pathology: A Revisit , 2019, International journal of molecular sciences.

[13]  H. Ulrich,et al.  Calcium signalling: A common target in neurological disorders and neurogenesis. , 2019, Seminars in cell & developmental biology.

[14]  M. Islam Calcium Signaling: From Basic to Bedside. , 2019, Advances in experimental medicine and biology.

[15]  C. Tabin,et al.  L-type voltage-gated Ca2+ channel CaV1.2 regulates chondrogenesis during limb development , 2019, Proceedings of the National Academy of Sciences.

[16]  P. Conaghan,et al.  Update on novel pharmacological therapies for osteoarthritis , 2019, Therapeutic advances in musculoskeletal disease.

[17]  A. Mobasheri,et al.  The Antihypertensive Drug Nifedipine Modulates the Metabolism of Chondrocytes and Human Bone Marrow-Derived Mesenchymal Stem Cells , 2019, Front. Endocrinol..

[18]  F. Barry,et al.  Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role of the Cell Secretome , 2019, Front. Bioeng. Biotechnol..

[19]  A. Arsenijević,et al.  Mesenchymal stem cell-based therapy of osteoarthritis: Current knowledge and future perspectives. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[20]  F. Figueroa,et al.  Umbilical Cord‐Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial , 2018, Stem cells translational medicine.

[21]  A. Mobasheri,et al.  The Role of Physical Stimuli on Calcium Channels in Chondrogenic Differentiation of Mesenchymal Stem Cells , 2018, International journal of molecular sciences.

[22]  T. Isho,et al.  Effectiveness of mesenchymal stem cells for treating patients with knee osteoarthritis: a meta-analysis toward the establishment of effective regenerative rehabilitation , 2018, npj Regenerative Medicine.

[23]  G. Suryakumar,et al.  Role of defective Ca2+ signaling in skeletal muscle weakness: Pharmacological implications , 2018, Journal of Cell Communication and Signaling.

[24]  M. Djamgoz,et al.  Mesenchymal stem cell differentiation: Control by calcium‐activated potassium channels , 2018, Journal of cellular physiology.

[25]  A. Mobasheri,et al.  The chondrocyte channelome: A narrative review. , 2018, Joint, bone, spine : revue du rhumatisme.

[26]  D. Harvanova,et al.  Influence of Kartogenin on Chondrogenic Differentiation of Human Bone Marrow-Derived MSCs in 2D Culture and in Co-Cultivation with OA Osteochondral Explant , 2018, Molecules.

[27]  D. Saris,et al.  Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration In Vitro , 2018, Theranostics.

[28]  P. Fernández-Pernas,et al.  CD105+-mesenchymal stem cells migrate into osteoarthritis joint: An animal model , 2017, PloS one.

[29]  A. Mobasheri,et al.  The role of metabolism in the pathogenesis of osteoarthritis , 2017, Nature Reviews Rheumatology.

[30]  A. Caplan Mesenchymal Stem Cells: Time to Change the Name! , 2017, Stem cells translational medicine.

[31]  Zhiguo Yuan,et al.  Advances and Prospects in Stem Cells for Cartilage Regeneration , 2017, Stem cells international.

[32]  Liwu Fu,et al.  Targeting calcium signaling in cancer therapy , 2016, Acta pharmaceutica Sinica. B.

[33]  M. Karsdal,et al.  Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future. , 2016, Osteoarthritis and cartilage.

[34]  Ali Mobasheri,et al.  An update on the pathophysiology of osteoarthritis. , 2016, Annals of physical and rehabilitation medicine.

[35]  P. Paez,et al.  Conditional Deletion of the L-Type Calcium Channel Cav1.2 in Oligodendrocyte Progenitor Cells Affects Postnatal Myelination in Mice , 2016, The Journal of Neuroscience.

[36]  E. Carafoli,et al.  Why Calcium? How Calcium Became the Best Communicator* , 2016, The Journal of Biological Chemistry.

[37]  Zhigang Xue,et al.  Cav1.2 of L-type Calcium Channel Is a Key Factor for the Differentiation of Dental Pulp Stem Cells. , 2015, Journal of endodontics.

[38]  Youngmee Jung,et al.  In Situ Recruitment of Human Bone Marrow-Derived Mesenchymal Stem Cells Using Chemokines for Articular Cartilage Regeneration , 2015, Cell transplantation.

[39]  Ivana Y. Kuo,et al.  Signaling in muscle contraction. , 2015, Cold Spring Harbor perspectives in biology.

[40]  Arnold I Caplan,et al.  Chondrogenic differentiation of mesenchymal stem cells: challenges and unfulfilled expectations. , 2014, Tissue engineering. Part B, Reviews.

[41]  A. Mobasheri,et al.  Regulation of chondrogenesis by protein kinase C: Emerging new roles in calcium signalling. , 2014, Cellular signalling.

[42]  B. Christ,et al.  Human Bone Marrow Mesenchymal Stem Cell-Derived Hepatocytes Improve the Mouse Liver after Acute Acetaminophen Intoxication by Preventing Progress of Injury , 2014, International journal of molecular sciences.

[43]  T. Neogi,et al.  The epidemiology and impact of pain in osteoarthritis. , 2013, Osteoarthritis and cartilage.

[44]  B. Alman,et al.  Specification of chondrocytes and cartilage tissues from embryonic stem cells , 2013, Development.

[45]  S. Heximer,et al.  Catharanthine Dilates Small Mesenteric Arteries and Decreases Heart Rate and Cardiac Contractility by Inhibition of Voltage-Operated Calcium Channels on Vascular Smooth Muscle Cells and Cardiomyocytes , 2013, The Journal of Pharmacology and Experimental Therapeutics.

[46]  A. Caselli,et al.  Isolation, Characterization, and Transduction of Endometrial Decidual Tissue Multipotent Mesenchymal Stromal/Stem Cells from Menstrual Blood , 2013, BioMed research international.

[47]  A. Mantalaris,et al.  Disease-modifying osteoarthritis drugs: in vitro and in vivo data on the development of DMOADs under investigation , 2013, Expert opinion on investigational drugs.

[48]  F. Guilak,et al.  Stem cell-based therapies for osteoarthritis: challenges and opportunities , 2013, Current opinion in rheumatology.

[49]  F. Barry,et al.  Strategies for improved targeting of therapeutic cells: implications for tissue repair. , 2012, European cells & materials.

[50]  H. Nejadnik,et al.  Autologous Bone Marrow–Derived Mesenchymal Stem Cells Versus Autologous Chondrocyte Implantation , 2010, The American journal of sports medicine.

[51]  F. Zou,et al.  Is iPS cell the panacea? , 2010, IUBMB life.

[52]  L. Csernoch,et al.  Ionotropic purinergic receptor P2X4 is involved in the regulation of chondrogenesis in chicken micromass cell cultures. , 2009, Cell calcium.

[53]  Hao Wang,et al.  Endometrial regenerative cells: A novel stem cell population , 2007, Journal of Translational Medicine.

[54]  C. Bony,et al.  Phenotypic and functional characterisation of ovine mesenchymal stem cells: application to a cartilage defect model , 2007, Annals of the rheumatic diseases.

[55]  M. Farach-Carson,et al.  Expression of voltage sensitive calcium channel (VSCC) L‐type Cav1.2 (α1C) and T‐type Cav3.2 (α1H) subunits during mouse bone development , 2005 .

[56]  L. Munaron,et al.  Intracellular calcium signals and control of cell proliferation: how many mechanisms? , 2004, Journal of cellular and molecular medicine.

[57]  J. Piriz,et al.  Nifedipine-Mediated Mobilization of Intracellular Calcium Stores Increases Spontaneous Neurotransmitter Release at Neonatal Rat Motor Nerve Terminals , 2003, Journal of Pharmacology and Experimental Therapeutics.

[58]  S. Ichinose,et al.  Characterization of Ca(2+) signaling pathways in human mesenchymal stem cells. , 2002, Cell calcium.

[59]  S. Matsumoto,et al.  Spontaneous calcium transients are required for neuronal differentiation of murine neural crest. , 1999, Developmental biology.

[60]  W. Klaus,et al.  Nifedipine and Bay K 8644 Induce an Increase of [Ca2+] i and Nitric Oxide in Endothelial Cells , 1999, Journal of cardiovascular pharmacology and therapeutics.

[61]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[62]  H. Schulman,et al.  Calcium/Calmodulin-dependent Phosphorylation and Activation of Human Cdc25-C at the G2/M Phase Transition in HeLa Cells* , 1999, The Journal of Biological Chemistry.

[63]  R. Fields,et al.  Gene regulation by patterned electrical activity during neural and skeletal muscle development , 1999, Current Opinion in Neurobiology.

[64]  M. Mattson,et al.  Alzheimer’s Presenilin Mutation Sensitizes Neural Cells to Apoptosis Induced by Trophic Factor Withdrawal and Amyloid β-Peptide: Involvement of Calcium and Oxyradicals , 1997, The Journal of Neuroscience.

[65]  C. Ohlsson,et al.  Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. , 1994, The New England journal of medicine.

[66]  A. Morgan,et al.  Ionomycin enhances Ca2+ influx by stimulating store-regulated cation entry and not by a direct action at the plasma membrane. , 1994, The Biochemical journal.

[67]  S. Yoshida,et al.  Mechanism of release of Ca2+ from intracellular stores in response to ionomycin in oocytes of the frog Xenopus laevis. , 1992, The Journal of physiology.

[68]  R. Narcisi,et al.  Expansion and Chondrogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells. , 2021, Methods in molecular biology.

[69]  A. Mobasheri,et al.  Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes , 2019, Current opinion in rheumatology.

[70]  C. Morris Cytotoxic Swelling of Sick Excitable Cells - Impaired Ion Homeostasis and Membrane Tension Homeostasis in Muscle and Neuron. , 2018, Current topics in membranes.

[71]  A. Mobasheri,et al.  The Potency of Induced Pluripotent Stem Cells in Cartilage Regeneration and Osteoarthritis Treatment. , 2018, Advances in experimental medicine and biology.

[72]  Joseph L Greenstein,et al.  Modeling calcium regulation of contraction, energetics, signaling, and transcription in the cardiac myocyte , 2016, Wiley interdisciplinary reviews. Systems biology and medicine.

[73]  Csaba Matta,et al.  Calcium signalling in chondrogenesis: implications for cartilage repair. , 2013, Frontiers in bioscience.

[74]  J. Welter,et al.  Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells: tips and tricks. , 2011, Methods in molecular biology.