Enhancement of sparc (osteonectin) synthesis in arthritic cartilage: Increased levels in synovial fluids from patients with rheumatoid arthritis and regulation by growth factors and cytokines in chondrocyte cultures

Abstract

Objective. To investigate the roles of SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) in arthritis, using cartilage and synovium specimens and synovial fluids (SF) from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), and to examine the effects of cytokines, growth factors, and hormones on SPARC synthesis by chondrocytes in culture.Methods. SPARC in cartilage and synovium was immunostained with monoclonal antibodies. SPARC synthesis by cultured chondrocytes was measured by Northern blot analysis, immunoblotting, and sandwich enzyme-linked immunosorbent assay.Results. SPARC was identified in numerous chondrocytes in the superficial and middle zones and in Shigeo Nakamura, DDS, Hisashi Satakeda, DDS, Hiroshi Okamoto, DDS, PhD, Mitsuhide Noshiro, PhD, Yukio Kato, DDS, PhD: Hiroshima University, Hiroshima, Japan; Kyouko Kamihagi, PhD, Masahiko Katayama, PhD: Biotechnology Research Laboratones, Takara Shyuzo, Ohtu, Japan; Haiou Pan, DDS: Drug Discovery Research Laboratories, Hoechst Japan Limited, Kawagoe, Japan; Koichiro Takahashi, PhD: Clinical Pharmacology Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Itabashi-ku, Tokyo, Japan; Yasuo Yoshihara, MD, Masayuki Shimmei, MD: National Defense Medical College, Tokorozawa, Japan; Yasunori Okada, MD, PhD: Cancer Research Institute, Kanazawa University, Kanazawa, Japan.Address reprint requests to Yukio Kato, DDS, PhD, Department of Biochemistry, School of Dentistry, Hiroshima University, 1-2-3, Kasumi, Minamiku, Hiroshima City, 734, Japan.Submitted for publication May 11, 1995; accepted in revised form November 6, 1995.regenerating chondrocytes of RA and OA joints, whereas such staining was absent in these zones of normal cartilage, except For weak signals from a few chondrocytes in the deep zone. In addition, SPARC synthesis was enhanced in synovial cells of RA and OA joints. The average SPARC level in SF was 10-fold higher in the RA than in the OA population. In rabbit articular chondrocyte cultures, administration of transforming growth factor pl (TGFp1) and bone morphogenetic protein 2 increased SPARC levels at 24-48 hours, whereas interleukin-lp (IL-lp), IL-la, tumor necrosis factor a, lipopolysaccharide, phorbol myristate acetate, basic fibroblast growth factor, and dexamethasone decreased SPARC levels at 2&72 hours. TGFP increased SPARC messenger RNA (mRNA) levels at 24 hours, whereas IL-IP caused a marked decrease in SPARC mRNA levels at 24 hours. Furthermore, IL-1 decreased the glycosylation of SPARC. Conclusion. These findings suggest that various growth factors and cytokines, including TGFm and IL-lp, regulate the production of SPARC by chondrocytes at pre-and posttranslational levels, and that SPARC synthesis is markedly enhanced in arthritic joints.SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) (BM-40) is a 3543-kd Ca++-binding glycoprotein, which was initially isolated from 539

Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair

“…Cartilage repair could be mediated by SPARC (osteonectin), an extracellular matrix protein involved in cartilage synthesis, which is overproduced by synovial cells from RA tissues. 29 Another class of tissue remodeling genes that is expressed at higher levels in these tissues is represented by genes encoding for proteins involved in wingless (wnt) signalling; wnt5a, Secreted Frizzled-related protein 2 (SFRP2), and Dickkopf homologue 3 (DKK3). The wnt signaling pathway has been characterized in drosophila and is important for embryonic limb development, cell growth and differentiation and its expression is developmentally regulated in a precise temporal and spatial manner.…”

Association of novel polymorphisms with the expression of SPARC in normal fibroblasts and with susceptibility to scleroderma

“…Alterations in SPARC expression appear to correlate with tumor metastasis and progression (10)(11)(12)(13). Increased SPARC expression is also observed in rheumatoid arthritis and osteoarthritis synovial tissue (14), as well as in hepatic cirrhosis and pulmonary fibrosis (15,16). One previous study has reported increased SPARC RNA levels (measured by Northern blotting) in SSc fibroblasts (17).…”

Biochemical Mediators Involved in Cartilage Degradation and the Induction of Pain in Osteoarthritis

“…Articular chondrocytes synthesize osteonectin, and this process is regulated by endogenous stimuli. IL-1, TNF-, and FGF-2, but not IL-6, greatly inhibit osteonectin expression (119,120). IL-1 also impairs the glycosylation of osteonectin (120).…”