ArticleApplied biochemistry and biotechnology2026
Syndecan-2 Regulates Integrin-β1 to Influence the Abnormal Subchondral Bone in Early-stage Knee Osteoarthritis.
Article in Applied biochemistry and biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIn osteoarthritis (OA), syndecan-2 (SDC-2) was found to be mainly present in blood vessels. This study was designed to investigate the expression of SDC-2 in subchondral bone during the early stage of knee OA and a possible mechanism underlying its role in early-stage OA.
methodsA rat knee OA model was established by performing the destabilization of the medial meniscus (DMM) surgery. In the early OA model at 2 weeks, 4 weeks, and 6 weeks time points, the platelet-derived growth factor-BB (PDGF-BB), platelet-derived growth factor receptor β (PDGFR-β), SDC-2, and integrin-β1 in the subchondral bone were observed using immunofluorescence. In vitro experiments, different concentrations of TR-14035 (0, 2.5, 5 µM) were used to treat the interleukin (IL)-1β-induced osteoclasts to analyze the changes of SDC-2 and p-Akt (Ser473)/Akt, and then cultured with endothelial progenitor cells (EPCs) to analyze the changes of PDGF-BB/PDGFR-β and p-NF-κB p65 (Ser536)/NF-κB p65 in EPCs. Moreover, exogenous SDC-2 was used to analyze its effects on integrin-β1 in IL-1β-induced osteoclasts and articular chondrocytes. Additionally, inhibition of integrin-β1 in early-stage OA rats was used to observe the changes of cartilage degeneration using Safranin O and collagen Ⅱ staining.
resultsThe expressions of PDGF-BB, PDGFR-β, SDC-2, and integrin-β1 in the subchondral bone of OA rats were significantly increased over time compared with the sham rats (P < 0.05). In the IL-1β-induced osteoclasts, TR-14035 treatment significantly reduced the IL-1β-induced increase in SDC-2, integrin β1, and p-Akt(Ser473)/Akt in a dose-dependent manner (P < 0.05). The PDGF-BB/PDGFR-β and p-NF-κB p65 (ser536)/NF-κB p65 pathways in EPCs were significantly enhanced after coculturing with IL-1β-induced osteoclasts, but inhibition of integrin β1 in IL-1β-induced osteoclasts attenuated the above effects (P < 0.05). Moreover, inhibition of integrin β1 improved the cartilage degradation in IL-1β-induced articular chondrocytes and early-stage OA rats, but exogenous SDC-2 attenuated these effects.
conclusionThis study showed SDC-2 regulated integrin-β1 in the IL-1β-induced osteoclasts to affect the endothelial PDGF-BB/PDGFR-β signaling. Inhibition of integrin β1 improved the cartilage degradation in IL-1β-induced articular chondrocytes and early-stage OA rats. This study suggested SDC-2/integrin-β1 played a critical role in subchondral bone during the early-stage OA.
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