Fibroblast growth factor 7 (FGF7) causes cartilage destruction, subchondral bone remodeling, and the premature growth plate closure in mice.

OBJECTIVE

Fibroblast growth factor (FGF) signaling plays a significant role in osteoarthritis (OA) pathogenesis, though the OA-related functions of only a few FGFs have been fully elucidated. This study investigates the specific roles of FGF7 in OA development.

METHODS

FGF7 expression was analyzed in human (n=6) and mouse (n=10) cartilage. Experimental OA was induced by destabilization of the medial meniscus (DMM). The roles of FGF7 were explored using intra-articular (IA) injection of recombinant FGF7 (rFGF7) and whole-body Fgf7 knockout mice (Fgf7-/-). Subchondral bone remodeling and growth plate morphology were assessed micro computed tomography (µCT) and histological analysis.

RESULTS

FGF7 was upregulated in OA cartilage. IA injection of rFGF7 led to OA cartilage destruction (OARSI [Osteoarthritis Research Society International] grade; 0.61 [95% CI 0.00-5.33]), while Fgf7-/- mice showed reduced DMM-induced cartilage erosion (OARSI grade; 1.89 [95% CI 1.08-3.00]) compared to wild-type mice (4.92 [95% CI 3.83-5.33]). These effects were associated with changes in matrix-degrading enzyme expression in chondrocytes. Mice receiving IA injection of rFGF7 (20 μg) exhibited increased subchondral bone thickness (68.01 µm [95% CI 61.55-74.46]) and decreased osteoclastogenesis (tartrate-resistant acid phosphatase positivity; 1.94% [95% CI 1.41-2.47]) compared to controls (38.33 µm [95% CI 33.71-42.96]) and (4.23% [95% CI 3.28-5.19]), respectively. Additionally, rFGF7 treatment caused premature closure of growth plates, whereas Fgf7-/- mice exhibited significantly increased growth plate thickness.

CONCLUSIONS

FGF7 exerts multiple functions in various joint tissues, including promoting cartilage destruction, inducing subchondral bone remodeling (SBP thickening), and triggering premature growth plate closure.