Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy.

Abstract

Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that is frequently associated with secondary osteoporosis. Previous studies have shown that TGFbeta inactivating antibody improves the muscle phenotype in mdx mice, a model of DMD. In the present study, we assessed the skeletal effects of treatment with a bone-targeted TGFbeta antibody (PCT-011) in mdx mice. Micro-computed tomography showed that 8 weeks of intraperitoneal administration of PCT-011 (10 mg per kg body mass, 3 times per week) was associated with more than twofold higher trabecular bone volume at the distal femur, which was explained by a higher trabecular number. At the femoral midshaft, PCT-011 exposure increased cortical thickness but did not significantly affect the results of three-point bending tests. Histomorphometric analyses of the lumbar vertebra 4 showed that PCT-011 treatment led to a lower bone formation rate. In conclusion, treatment with the TGFbeta antibody PCT-011 had a positive effect on bone development in mdx mice. Inhibiting TGFbeta activity thus appears to be a promising approach to treat bone fragility in the context of DMD.

• Authors: Juliana Marulanda, Iris Boraschi-Diaz, Pierre Beauparlant, Philippe Crine, Frank Rauch
• Journal: Life (Basel, Switzerland) (Life (Basel)) Vol. 11 Issue 8 (Aug 05 2021) ISSN: 2075-1729 [Print] Switzerland
• PMID: 34440535 (Publication Type: Journal Article)