CK2.1 Activates Chondrogenesis by Regulation of the p38 Mitogen-Activated Protein Kinase Pathway

Osteoarthritis (OA) remains a challenging disease due to the increased rate of incidence in the older population and the lack of a disease-modifying drug. BMP signaling plays a crucial role in chondrogenic differentiation and in the stability of articular cartilage. However, because BMP-2 also induces chondrocyte hypertrophy, it is not a viable drug for OA treatment. In contrast, the Bmpr1a biomimetic peptide can repair articular cartilage without inducing chondrocyte hypertrophy in the OA mouse model and in chondrocytes derived from patients diagnosed with OA. Despite this benefit, the mechanism by which the peptide drives chondrogenesis remains elusive. To explore this, we use a phosphoproteomics approach to identify pathways differentially activated by CK2.1. Specifically, we identified differentially phosphorylated phosphosites by CK2.1. Based on these phosphosites that we identified, we propose a molecular mechanism by which CK2.1 activates chondrogenesis. Notably, we predict that the mitogen-activated protein kinase (MAPK) pathway is regulated by CK2.1 to induce proteoglycan synthesis in C3H10T1/2 cells.