GDF-5 is suppressed by IL-1beta and enhances TGF-beta3-mediated chondrogenic differentiation in human rheumatoid fibroblast-like synoviocytes.

To investigate the expression of growth differentiation factor-5 (GDF-5) in chondrocytes (HC) and fibroblast-like synoviocytes (FLS) from humans with rheumatoid arthritis (RA) when stimulated with proinflammatory cytokines and to explore whether GDF-5 plays a role in regulating the differentiation of FLS-RA into chondrocytes. Expression of GDF-5 in synovium and cartilage in RA and osteoarthritis (OA) was assessed by immunohistochemistry. GDF-5 production in FLS-RA and HC-RA was examined through real-time quantitative RT-PCR (Q-PCR) and western blotting. Expressions of GDF-associated receptors on FLS-RA were determined by semiquantitative-PCR, and MTT assay was used to study the effects on FLS-RA proliferation. Effect of GDF-5 and TGF-beta3 on in vitro chondrogenic ability of FLS-RA was investigated using pellet-culture system, Q-PCR and histological analysis. Immunohistochemical analysis demonstrated that GDF-5 expression in the synovium and cartilage from joints of RA patients was much lower than that of OA patients. Addition of IL-1beta or TNF-alpha appeared to downregulate the expression of GDF-5 in HC-RA and FLS-RA. Inhibition of GDF-5 expression by IL-1beta in RA-FLS was attenuated by pretreatment with MEK1/2 inhibitor. GDF-5-associated receptors were expressed in FLS-RA, but GDF-5 had no effect on FLS-RA proliferation. GDF-5 had a strong chondrogenic-promoting effect on TGF-beta3-induced chondrocyte differentiation in FLS-RA. GDF-5 is expressed in FLS-RA and HC-RA, and its expression is strongly downregulated by proinflammatory cytokines. MEK-ERK pathway is a negative regulator of GDF-5 expression in FLS-RA. In FLS-RA, synergy between GDF-5 and TGF-beta3 enhances chondrogenesis. Anti-inflammatory drugs combined with GDF-5 might be a new therapeutic treatment for RA.

Liu FL ，Lin LH ，Sytwu HK ，Chang DM ... -  《-》

Modulatory effects of inflammation and therapy on GDF-5 expression in rheumatoid arthritis synovium.

Bramlage CP ，Kaps C ，Ungethüm U ，Bramlage P ，Koziolek M ，Wessels J ，Krenn V ，Pruss A ，Müller GA ，Strutz F ，Burmester GR ，Häupl T ... -  《-》

Interleukin (IL)-23 p19 expression induced by IL-1beta in human fibroblast-like synoviocytes with rheumatoid arthritis via active nuclear factor-kappaB and AP-1 dependent pathway.

Liu FL ，Chen CH ，Chu SJ ，Chen JH ，Lai JH ，Sytwu HK ，Chang DM ... -  《RHEUMATOLOGY》

Kappa and delta opioid receptors are expressed but down-regulated in fibroblast-like synoviocytes of patients with rheumatoid arthritis and osteoarthritis.

Shen H ，Aeschlimann A ，Reisch N ，Gay RE ，Simmen BR ，Michel BA ，Gay S ，Sprott H ... -  《ARTHRITIS AND RHEUMATISM》

Responses to the proinflammatory cytokines interleukin-1 and tumor necrosis factor alpha in cells derived from rheumatoid synovium and other joint tissues involve nuclear factor kappaB-mediated induction of the Ets transcription factor ESE-1.

Grall F ，Gu X ，Tan L ，Cho JY ，Inan MS ，Pettit AR ，Thamrongsak U ，Choy BK ，Manning C ，Akbarali Y ，Zerbini L ，Rudders S ，Goldring SR ，Gravallese EM ，Oettgen P ，Goldring MB ，Libermann TA ... -  《ARTHRITIS AND RHEUMATISM》