Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China.
Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
J Orthop Surg Res. 2023 Mar 13;18(1):199. doi: 10.1186/s13018-023-03658-z.
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.
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.
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.
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.
软骨细胞增殖和分化的紊乱是骨关节炎（OA）关节损伤过程中的一个关键事件。P-15 肽可以与各种前体细胞上的整合素受体结合，促进细胞黏附、释放生长因子，并促进成骨前体细胞的分化。然而，P-15 在 OA 中的作用，特别是在软骨细胞增殖中的作用，尚未完全阐明。
采用实时定量聚合酶链反应（qRT-PCR）分析骨关节炎患者骨组织中 SFPQ 和 RUNX2 的活性。采用白细胞介素-1β（IL-1β）诱导剂建立 OA 的体外模型。通过 CCK-8 法测定细胞增殖。采用 qRT-PCR 检测 COL2a1、ACAN、COMP、SOX9 和 BMP2 等与软骨分化相关的基因表达。此外，采用 Western blot 检测 SFPQ、AKT、p-AKT 和 RUNX2 的表达水平。
结果表明，OA 软骨组织中 SFPQ 的表达明显降低，RUNX2 的表达明显升高。P-15 肽可逆转 IL-1β诱导的细胞增殖障碍，减轻软骨细胞损伤。此外，P-15 多肽以剂量依赖的方式增加软骨分化基因 COL2a1、ACAN 和 BMP2 的表达水平，同时降低 COMP 和 SOX9 的表达水平。然后，特异性干扰 RNA 证明 P-15 维持软骨细胞稳定性，与 SFPQ 基因有关。最后，我们证实 P-15 通过抑制 Akt-RUNX2 通路来抑制细胞死亡，调节 SFPQ 的表达，从而减轻软骨细胞损伤和骨关节炎的进展。
P-15 通过抑制细胞死亡和调节 SFPQ-Akt-RUNX2 通路，减轻软骨细胞损伤和骨关节炎进展，为治疗骨关节炎提供了新的策略。
