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Effect of Anti‐TGF‐β Treatment in a Mouse Model of Severe Osteogenesis Imperfecta
Author(s) -
Tauer Josephine T,
Abdullah Sami,
Rauch Frank
Publication year - 2019
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3617
Subject(s) - osteogenesis imperfecta , endocrinology , alkaline phosphatase , medicine , neutralizing antibody , acid phosphatase , bone resorption , transforming growth factor , bone mineral , antibody , chemistry , immunology , osteoporosis , enzyme , pathology , biochemistry
Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I encoding genes. Recent studies in mouse models of recessive OI, Crtap ‐/‐ mice, and dominant OI, +/G610C mice, found that application of a transforming growth factor beta (TGF‐β) neutralizing antibody 1D11 rescues the bone phenotype. In the present study, we investigated TGF‐β signaling in a mouse model of severe dominant OI with a high incidence of spontaneous fractures, Col1a1 Jrt/+ mice, and the effect of TGF‐β neutralizing antibody 1D11 on bone phenotype in 8‐week‐old mice. Col1a1 Jrt/+ mice had elevated TGF‐β signaling in bone tissue. Treatment of Col1a1 Jrt/+ mice with 1D11 was associated with increased bone length but had no significant effect on bone mass or bone mechanical properties, and no significant treatment‐associated differences in serum markers of bone formation (alkaline phosphatase activity) or resorption (tartrate‐resistant acid phosphatase) were found. Our data thus indicate that the TGF‐β neutralizing antibody 1D11 is not effective in a mouse model of dominant OI with a high incidence of spontaneous fractures. © 2018 American Society for Bone and Mineral Research.