Hydroxychloroquine (HCQ) induces inhibition of Col-II and COMP expression in the chondrocytes

Tao Li,Li-Ting Zhang,Chang-Jun Dong,Guang Yang,Bin Li

doi:10.3329/bjp.v11i2.24882

Abstract

<p>Osteoarthritis (OA) is the disease of joints which results in articular cartilage degradation and remodeling of bones accompanied by joint pain and stiffness. Chloroquine (CQ) analogs like hydroxychloroquine have been used for the treatment of systemic lupus rheumatoid polyarthritis and erythematosus. The present study was aimed to investigate the effect of hydroxychloroquine (HCQ) on the level of collagen type II (Col-II) and oligomeric matrix protein COMP expression in chondrocytes of knee osteoarthritis. The rate of growth in cartilage cells was analyzed using MTT assay where as the Col-2 and COMP expression levels were detected by RT-PCR and western blotting analyses. For the determination of MMP-13 expression, ELISA test was used. The results revealed a no significant change in the rate of cartilage cell proliferation in HCQ treated compared to the untreated cells. HCQ treatment exhibited concentration and time-dependent effect on the inhibition of Col-2 and COMP expression in chondrocytes. However, its treatment caused a significant enhancement in the expression levels of MMP-13 compared to the untreated cells. Therefore, HCQ promotes expression of MMP-13 and reduces Col-2 and COMP expression levels in the chondrocytes without any significant change in the growth of the cells.</p><p> </p>

Highlights

Osteoarthritis is the disease of joints which results in articular cartilage degradation and remodeling of bones accompanied by joint pain and stiffness (Wattanachai et al, 2009: Gentili and Cancedda, 2009)
The present study demonstrates the effect of hydroxychloroquine on the chondrocytes of knee osteoarthritis
The results showed that hydroxychloroquine treatment inhibited the expression of both collagen type II and COMP in chondrocytes after 36 hours (Table II)

Summary

Introduction

Osteoarthritis is the disease of joints which results in articular cartilage degradation and remodeling of bones accompanied by joint pain and stiffness (Wattanachai et al, 2009: Gentili and Cancedda, 2009). The non-proliferating chondrocytes produce a large amount of extracellular matrix which mainly consists of two types of macromolecules, collagens (types II, IX and XI) and proteoglycans. Chondrocytes are responsible for the synthesis of sufficient quantity of the extracellular matrix molecules for establishing the cartilage homeostasis (Goldring, 2000; Roughley, 2001). Cartilage extracellular matrix molecules such as type II collagen and sulfated proteogly can play a crucial role in regulating chondrocyte functions by mediating interaction between cell and matrix (Eyre, 2002). Degeneration of articular cartilage by inhibition of chondrocyte function is the major cause of cartilage diseases like osteoarthritis and rheumatoid arthritis (Cawston et al, 1999; Kim and Song, 1999). Promotion of chondrocyte proliferation can exhibit an important effect on the management of cell functions

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