Mouse Study Links FGFR3 Mutation to Musculoskeletal Aging

A mouse model of hypochondroplasia showed changes in cartilage, bone, and skeletal muscle, along with disrupted mitochondrial pathways, according to an abstract for the American Society for Bone and Mineral Research (ASBMR) 2026 meeting, scheduled for October 9–12.

The investigators studied Fgfr3N534K/+ mice at multiple ages and compared them with Fgfr3+/+ mice. They measured articular cartilage and subchondral bone, quantified collagen fibers, assessed bone by micro–computed tomography and proteomics, and examined skeletal muscle using grip testing, RT-qPCR, and immunofluorescence. The abstract does not state how many mice were studied.

In the medial tibial plateau, mutant mice had thinner articular cartilage and thicker collagen fibers than wild-type mice. Their subchondral bone had higher bone mineral density, bone volume fraction, and trabecular number. The authors described these findings as osteoarthritis-like changes and suggested increased subchondral bone remodeling.

The mutant mice also had reduced muscle force and smaller muscle fiber cross-sectional area, along with a higher shape factor index. TRIM63 expression was significantly lower. The authors interpreted these results as evidence of structural and functional muscle changes and suggested that disrupted protein turnover could contribute to impaired muscle homeostasis.

In older mutant mice, femoral scans showed higher cortical tissue mineral density and bone volume fraction, but lower trabecular bone mineral density and bone volume fraction, compared with wild-type mice. The authors said the greater disruption of bone parameters in mutant mice indicated increased fragility.

Proteomic analysis of cortical bone from 3 to 24 months identified mutation-specific disruption of mitochondrial pathways, particularly oxidative phosphorylation and the tricarboxylic acid cycle. The authors reported an early increase in mitochondrial pathway activity in mutant mice and interpreted it as part of an accelerated aging trajectory. They proposed mitochondrial dysfunction as a potential mechanism for premature musculoskeletal aging in this mouse model. The abstract does not provide statistical estimates for most comparisons.

Reference

Fayad C, Tamáš M, Gatto G, et al. Mitochondrial dysfunction plays a key role in premature musculoskeletal aging in hypochondroplasia mouse model. Abstract for the American Society for Bone and Mineral Research (ASBMR) 2026 meeting; October 9-12, 2026. https://eppro01.ativ.me/web/page.php?page=Session&project=ASBMR26&id=p7435-441