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

Abstract

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.

Keywords: Cartilage; Chondrocytes; FGF7; Growth plate; Osteoarthritis; Subchondral bone.