Upregulated GDF-15 in Ankylosing Spondylitis: Pathologic Ossification Promotion through Ligament Fibroblast...

Area of Science:

• Rheumatology and Immunology
• Molecular Biology
• Biochemistry

Background:

• Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by new bone formation.
• The role of growth differentiation factor 15 (GDF-15) in AS pathogenesis, particularly in new bone formation, remains unclear.

Purpose of the Study:

• To investigate the role of GDF-15 in AS.
• To elucidate the mechanism by which GDF-15 influences osteogenesis in AS.

Main Methods:

• Established a proteoglycan-induced arthritis mouse model for AS.
• Quantified GDF-15 expression in serum and spinal tissues using ELISA and immunohistochemistry.
• Assessed the osteogenic differentiation of primary fibroblasts from healthy controls and AS patients in vitro using Western blotting, ALP, and alizarin red staining.

Main Results:

• GDF-15 expression was significantly upregulated in the AS mouse model.
• GDF-15 promoted osteogenic differentiation in both healthy control and AS fibroblasts.
• In AS fibroblasts, GDF-15 enhanced osteogenic marker gene expression and activated the Wnt/β-catenin signaling pathway, an effect reversible by DKK-1.

Conclusions:

• Aberrant GDF-15 upregulation in AS contributes to new bone formation.
• GDF-15 promotes osteogenesis in AS fibroblasts via the Wnt/β-catenin signaling pathway.
• GDF-15 represents a potential therapeutic target for managing new bone formation in AS.