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- Title
Tendon and motor phenotypes in the Crtap<sup>-/-</sup> mouse model of recessive osteogenesis imperfecta.
- Authors
William Grol, Matthew; Haelterman, Nele A.; Joohyun Lim; Munivez, Elda M.; Archer, Marilyn; Hudson, David M.; Tufa, Sara F.; Keene, Douglas R.; Lei, Kevin; Dongsu Park; Kuzawa, Cole D.; Ambrose, Catherine G.; Eyre, David R.; Lee, Brendan H.
- Abstract
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-b, inflammatory, and metabolic signaling. At 4-months, Crtap-/- mice showed increased aSMA, MMP2, and phospho-NFkB 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.
- Subjects
LABORATORY mice; PATELLAR tendon; OSTEOGENESIS imperfecta; PHENOTYPES; ANIMAL disease models; JOINT hypermobility; ACHILLES tendon
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.63488