Zhuangguguanjie formulation protects articular cartilage from degeneration in joint instability-induced murine knee osteoarthritis.

Zhuangguguanjie formulation (ZG) can provide noticeable relief from joint pain in patients suffering from knee osteoarthritis (OA). However, the underlying mechanism has not been fully described. Male C57BL/6 mice were administered either ZG or normal saline (NS) following surgical destabilization of the medial meniscus (DMM). At weeks 4, 6 and 8 (post-surgery), knee joints were harvested and assessed with Safranin-O staining. Blood serum was collected and tested. In vitro analysis was carried out to evaluate the effects of ZG on the expression of the OA-related genes. DMM mice indicated reduced cartilage destruction and lower blood serum biomarkers of OA (COMP1 and CTX-1) following ZG treatment. Moreover, the femoral condyle and tibial plateau histological scores were significantly reduced following ZG treatment of the DMM mice. ZG could markedly downregulate the expression of OA-related genes namely, ADAMTS5, MMP3 and MMP13, while it simultaneously upregulated collagen II as demonstrated by in vitro assays. Moreover, chondrocyte apoptosis was significantly decreased following ZG treatment. These results may be caused by the up-regulation of p-AKT expression levels, since the anti-apoptotic effects of ZG can be blocked by treatment with an AKT inhibitor. ZG is capable of preventing and/or reducing the progression of OA by inhibiting chondrocyte apoptosis via the p-AKT/Caspase 3 pathway.

[1]  Xiaoming Fan,et al.  Pretreatment with propylene glycol alginate sodium sulfate ameliorated concanavalin A‐induced liver injury by regulating the PI3K/Akt pathway in mice , 2017, Life sciences.

[2]  L. Nartey,et al.  Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis , 2017, The Lancet.

[3]  S. Barrile,et al.  Effect of aquatic physical therapy on pain perception, functional capacity and quality of life in older people with knee osteoarthritis: study protocol for a randomized controlled trial , 2017, Trials.

[4]  L. Troeberg,et al.  ADAMTS and ADAM metalloproteinases in osteoarthritis – looking beyond the ‘usual suspects’ , 2017, Osteoarthritis and cartilage.

[5]  Christopher Louizos,et al.  Glucosamine and chondroitin use in canines for osteoarthritis: A review , 2017, Open veterinary journal.

[6]  Z. Hadziahmetovic,et al.  Comparison of Clinical and Radiological Parameters at Knee Osteoarthritis , 2017, Medical archives.

[7]  Changqing Zhang,et al.  The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials , 2017, Journal of Orthopaedic Surgery and Research.

[8]  J. Kopec,et al.  Validation of Administrative Osteoarthritis Diagnosis Using a Clinical and Radiological Population-Based Cohort , 2016, International journal of rheumatology.

[9]  Y. Yoo,et al.  Alpha B-Crystallin Protects Rat Articular Chondrocytes against Casein Kinase II Inhibition-Induced Apoptosis , 2016, PloS one.

[10]  D C Spray,et al.  Strain-induced mechanotransduction through primary cilia, extracellular ATP, purinergic calcium signaling, and ERK1/2 transactivates CITED2 and downregulates MMP-1 and MMP-13 gene expression in chondrocytes. , 2016, Osteoarthritis and cartilage.

[11]  X. Weng,et al.  Efficacy and Safety of Zhuanggu Joint Capsules in Combination with Celecoxib in Knee Osteoarthritis: A Multi-center, Randomized, Double-blind, Double-dummy, and Parallel Controlled Trial , 2016, Chinese medical journal.

[12]  J. Cheong,et al.  Leptin protects rat articular chondrocytes from cytotoxicity induced by TNF-α in the presence of cyclohexamide. , 2015, Osteoarthritis and cartilage.

[13]  H. Zhan,et al.  The Effectiveness of Manual Therapy for Relieving Pain, Stiffness, and Dysfunction in Knee Osteoarthritis: A Systematic Review and Meta-Analysis. , 2015, Pain physician.

[14]  R. Klein,et al.  Cost-Effectiveness Analyses of Osteoarthritis Oral Therapies: a Systematic Review , 2013, Applied Health Economics and Health Policy.

[15]  N. Lin,et al.  Treatment with SiMiaoFang, an anti-arthritis chinese herbal formula, inhibits cartilage matrix degradation in osteoarthritis rat model. , 2013, Rejuvenation research.

[16]  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.

[17]  Pradeep Suri,et al.  Epidemiology of Osteoarthritis and Associated Comorbidities , 2012, PM & R : the journal of injury, function, and rehabilitation.

[18]  A. Luigi.  Complementary and Alternative Medicine in Osteoarthritis , 2012 .

[19]  Bing Zhang,et al.  Increased apoptosis in human knee osteoarthritis cartilage related to the expression of protein kinase B and protein kinase Cα in chondrocytes. , 2012, Folia histochemica et cytobiologica.

[20]  J. Hecht,et al.  D469del-COMP retention in chondrocytes stimulates caspase-independent necroptosis. , 2012, The American journal of pathology.

[21]  Y. Yoo,et al.  Downregulation of Protein Kinase CK2 Activity Facilitates Tumor Necrosis Factor-α-Mediated Chondrocyte Death through Apoptosis and Autophagy , 2011, PloS one.

[22]  H. Roach,et al.  Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. , 2011, European cells & materials.

[23]  R. Loeser,et al.  Biology and pathology of Rho GTPase, PI‐3 kinase‐Akt, and MAP kinase signaling pathways in chondrocytes , 2010, Journal of cellular biochemistry.

[24]  H. Im,et al.  Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes inhibits insulin-like growth factor 1-mediated cell survival and proteoglycan synthesis. , 2009, Arthritis and rheumatism.

[25]  Francis Berenbaum,et al.  Primary culture and phenotyping of murine chondrocytes , 2008, Nature Protocols.

[26]  L. Kang,et al.  [Clinical randomized controlled trial on splint external fixation combined with Chinese herbs in treating distal radius fractures of elderly patients]. , 2008, Zhongguo gu shang = China journal of orthopaedics and traumatology.

[27]  S. Schelling,et al.  Double-knockout of ADAMTS-4 and ADAMTS-5 in mice results in physiologically normal animals and prevents the progression of osteoarthritis. , 2007, Arthritis and rheumatism.

[28]  S. Glasson,et al.  The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. , 2007, Osteoarthritis and cartilage.

[29]  David W. Andrews,et al.  Embedded together: The life and death consequences of interaction of the Bcl-2 family with membranes , 2007, Apoptosis.

[30]  B. Cillero-Pastor,et al.  Cytokines, tumor necrosis factor-α and interleukin-1β, differentially regulate apoptosis in osteoarthritis cultured human chondrocytes , 2006 .

[31]  D. D’Lima,et al.  Caspase inhibitors reduce severity of cartilage lesions in experimental osteoarthritis. , 2006, Arthritis and rheumatism.

[32]  J. Ge,et al.  [Effect of compound duzhong jiangu granule on knee joint osteoarthritis: a report of 400 cases]. , 2005, Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine.

[33]  J. Chun,et al.  Signaling Mechanisms Leading to the Regulation of Differentiation and Apoptosis of Articular Chondrocytes by Insulin-like Growth Factor-1* , 2003, Journal of Biological Chemistry.

[34]  D. D’Lima,et al.  Human chondrocyte apoptosis in response to mechanical injury. , 2001, Osteoarthritis and cartilage.

[35]  K. Choe,et al.  Apoptotic chondrocyte death in human osteoarthritis. , 2000, The Journal of rheumatology.

[36]  M. Lotz,et al.  Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. , 1998, Arthritis and rheumatism.

[37]  B. Cillero-Pastor,et al.  Cytokines, tumor necrosis factor-alpha and interleukin-1beta, differentially regulate apoptosis in osteoarthritis cultured human chondrocytes. , 2006, Osteoarthritis and cartilage.