FOSL2 Promotes Chondrogenic Differentiation of Bone Marrow Mesenchymal Stem Cells via Upregulation of CAMK2D in Osteoarthritis.
Abstract
Background
FOSL2 has been linked to inflammation and tissue remodeling, but its role in osteoarthritis (OA) remains unclear. OA is characterized by progressive cartilage loss and limited regenerative capacity.
Methods
FOSL2 expression was first measured in cartilage samples from OA patients undergoing total knee arthroplasty. Bone marrow mesenchymal stem cells (BMSCs) were then induced to undergo chondrogenic differentiation in vitro. FOSL2 was knocked down or overexpressed, and downstream effects on chondrogenic and catabolic markers were assessed. CAMK2D was identified as a potential downstream target by RNA sequencing. Finally, FOSL2-knockdown BMSCs were injected intra-articularly into Sprague-Dawley rats with ACLT-induced OA.
Results
FOSL2 was lower in cartilage-defective areas than in relatively normal cartilage. During BMSC chondrogenic differentiation, FOSL2 was upregulated along with COLII and SOX9, whereas ADAMTS5, MMP13, and COL10 were downregulated. FOSL2 knockdown impaired chondrogenic potential. FOSL2 regulated CAMK2D expression. In vivo, FOSL2-knockdown BMSCs exhibited reduced cartilage repair capacity in rat OA joints.
Conclusions
FOSL2 promotes BMSC chondrogenic differentiation through CAMK2D and improves cartilage repair in OA. FOSL2 represents a potential therapeutic target for OA.