Background: microRNA (miR)-mediated post-transcriptional repression has been reported in the process of chondrocyte dysfunction. The present study aimed to investigate the molecular mechanisms underlying in oleanolic acid (OLA)-prevented interleukin (IL)-1β-induced chondrocyte dysfunction via the miR-148-3p/fibroblast growth factor-2 (FGF-2) signaling pathway.Methods: Candidate miRs were filtrated using miR microarray assays in chondrocytes with or without IL-1β stimulation. Gene expression of candidate miRs and protein expression of FGF2 were analyzed using a quantitative reverse transcriptasepolymerase chain reaction and western blotting, respectively. Cell growth was evaluated using cell counting kit-8 assays. Cell apoptosis was detected using Annexin V-fluorescein isothiocyanate double staining.Results: Treatment with OLA counteracted IL-1β-evoked chondrocyte growth inhibition, apoptosis, caspase3 production, and release of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine. Additionally, FGF2 protein expression levels elevated by IL-1β were down-regulated by OLA and transfection with miR-148-3p mimics. IL-1β-induced down-regulation of miR-148-3p in chondrocytes was evaluated by OLA administration. Bioinformatics algorithms and experimental measurements indicated that FGF2 might be a direct target of miR-148-3p. miR-148-3p mimics exhibited equal authenticity of OLA to protect against IL-1β-induced chondrocyte dysfunction. Conclusions:Our present findings highlight a protective effect of OLA on IL-1βinduced chondrocyte dysfunction, and a novel signal cascade comprising the miR-148-3p/FGF2 signaling pathway might be a potential therapeutic target of OLA with respect to preventing the progression of osteoarthritis.

Background The disruption of chondrocyte proliferation and differentiation is a critical event during the process of joint injury in osteoarthritis (OA). P-15 peptides could bind to integrin receptors on various precursor cells, promote cell adhesion, release growth factors, and promote the differentiation of osteoblast precursor cells. However, the role of P-15 in OA, particularly in chondrocyte proliferation, is not fully understood. Methods The activity of SFPQ and RUNX2 in the bone tissue of patients with osteoarthritis was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Interleukin-1β (IL-1β) inducer was performed to establish an in vitro model of OA. Cell proliferation was measured by CCK-8 assay. The expressions of COL2a1, ACAN, COMP, SOX9, and BMP2 related to cartilage differentiation were detected using qRT-PCR. In addition, the expression levels of SFPQ, AKT, p-AKT, and RUNX2 were detected using Western blotting. Results The results showed that the expression of SFPQ was significantly decreased and the expression of RUNX2 was significantly increased in osteoarthritis cartilage tissue. P-15 peptide reversed IL-1β-induced cell proliferation obstruction and alleviated chondrocyte damage. Furthermore, P-15 polypeptide increased the expression levels of cartilage differentiation genes COL2a1, ACAN, and BMP2, while decreasing the expression of COMP and SOX9 in an inverse dose-dependent manner. Then specific interfering RNA proved that P-15 maintains chondrocyte stability and is associated with the SFPQ gene. Finally, we confirmed that P-15 inhibited the Akt-RUNX2 pathway, which is regulated in the expression of SFPQ. Conclusions P-15 can mitigate chondrocyte damage and osteoarthritis progression by inhibiting cell death and modulating SFPQ-Akt-RUNX2 pathway, offering an opportunity to develop new strategies for the treatment of osteoarthritis.

Osteoporosis, a bone disease common in the elderly, results in bone loss and damage to bone microstructure. Sirtuin 1 (Sirt1), belongs to Sirtuin family, is involved in regulating bone quality. Circ-Sirt1 is one of the transcripts of Sirt1 host gene. Here, the involvement of circ-Sirt1 was determined in bone disease for the first time, proposing that circ-Sirt1 can activate the Wnt/β-catenin pathway to promote osteogenesis differentiation. This study was aimed to elucidate the potential function of Circ-Sirt1 and Sirt1 regulatory loop in the differentiation of bone marrow mesenchymal stem cells (BMSCs). The differentiation of bone marrow mesenchymal stem cells was detected by ALP, alizarin red staining and qPCR. The dual luciferase reporter assay was applied to reveal the interaction between RNAs. The result showed that Sirt1 promoted osteogenic differentiation of BMSCs. Circ-Sirt1, derived from Sirt1, acted as miR-132 and miR-212 sponge, and up-regulated the expression of Sirt1. Furthermore, Sirt1-mediated circ-Sirt1 promoted osteogenic differentiation. Finally, we unveiled that Circ-Sirt1 facilitates osteogenic differentiation by activating the Wnt/β-catenin pathway. In conclusion, our data suggested that Circ-Sirt1 elevates osteogenic differentiation via miR-132/212/Sirt1 and Wnt/β-catenin pathway.

Background The disruption of chondrocyte proliferation and differentiation is a critical event during the process of joint injury in osteoarthritis (OA). P-15 peptides could bind to integrin receptors on various precursor cells, promote cell adhesion, release growth factors, and promote the differentiation of osteoblast precursor cells. However, the role it plays in OA, particularly in chondrocyte proliferation, is not fully understood. Methods The activity of SFPQ and RUNX2 in the bone tissue of patients with osteoarthritis was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Interleukin-1β (IL-1β) inducer was performed to establish an in vitro model of OA. Cell proliferation was measured by CCK-8 assay. The expressions of COL2a1, ACAN, COMP, SOX9, and BMP2 related to cartilage differentiation were detected using qRT-PCR. In addition, the expression levels of SFPQ, AKT, p-AKT, and RUNX2 were detected using Western blotting. Results The results showed that the expression of SFPQ was significantly decreased and the expression of RUNX2 was significantly increased in osteoarthritis cartilage tissue. P-15 peptide reversed IL-1β-induced cell proliferation obstruction and alleviated chondrocyte damage. Furthermore, P-15 polypeptide increased the expression levels of cartilage differentiation genes COL2a1, ACAN, and BMP2, while decreasing the expression of COMP and SOX9 in an inverse dose-dependent manner. Then specific interfering RNA proved that P-15 maintains chondrocyte stability and is associated with the SFPQ gene. Finally, we confirmed that P-15 inhibited the Akt-SUNX2 pathway, which is regulated in the expression of SFPQ. Conclusions P-15 can mitigate chondrocyte damage and osteoarthritis progression by inhibiting cell death and modulating SFPQ-Akt-SUNX2 pathway, offering an opportunity to develop new strategies for the treatment of osteoarthritis.