P-15 promotes chondrocyte proliferation in osteoarthritis by regulating SFPQ to target the Akt-RUNX2 axis

• Published in: Journal of orthopaedic surgery and research 2023-03, Vol.18 (1), p.199-199, Article 199
• Main Authors: Li, Yuanli, Nie, Junlan, Deng, Changgong, Li, Hong
• Format: Article
• Language: English
• Subjects: AKT protein; Akt-RUNX2 axis; Analysis; Apoptosis; Arthritis; Bone morphogenetic protein 2; Cartilage; Cartilage diseases; Cbfa-1 protein; Cell adhesion; Cell adhesion & migration; Cell culture; Cell death; Cell differentiation; Cell proliferation; Cell Proliferation - genetics; Cholecystokinin; Chondrocytes; Chondrocytes - metabolism; Chondrogenesis; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Design; Extracellular matrix; Growth factors; Humans; IL-1β; Integrins; Interleukin-1beta - metabolism; Interleukins; Kinases; Medical research; Orthopedics; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoblastogenesis; P-15 peptide; Pathogenesis; Peptides; Polymerase chain reaction; Proliferation; Proteins; Proto-Oncogene Proteins c-akt - metabolism; SFPQ; Sox9 protein; Transcription factors; Variance analysis; Western blotting
• ISSN: 1749-799X; 1749-799X
• 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.