Tendon and motor phenotypes in the Crtap mouse model of recessive osteogenesis imperfecta

Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon dysfunction in OI pathogenesis is largely unknown. Using the Crtap mouse model of severe, recessive OI, we found that mutant Achilles and patellar tendons were thinner and weaker with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar tendons from Crtap mice also had altered numbers of CD146⁺CD200⁺ and CD146^-CD200⁺ progenitor-like cells at skeletal maturity. RNA-seq analysis of Achilles and patellar tendons from 1-month Crtap mice revealed dysregulation in matrix and tendon marker gene expression concomitant with predicted alterations in TGF-β, inflammatory, and metabolic signaling. At 4-months, Crtap mice showed increased αSMA, MMP2, and phospho-NFκB staining in the patellar tendon consistent with excess matrix remodeling and tissue inflammation. Finally, a series of behavioral tests showed severe motor impairments and reduced grip strength in 4-month Crtap mice - a phenotype that correlates with the tendon pathology.