About this Medicine article
Role of the Mitochondrial Permeability Transition in Bone Metabolism and Aging by Rubens Sautchuk; Chen Yu; Matthew McArthur; Christine Massie; Paul S. Brookes; George A. Porter; Hani Awad; Roman A. Eliseev is a Medicine article available to read on EtoBox.
The mitochondrial permeability transition pore (MPTP) and its positive regulator, cyclophilin D (CypD), play important pathophysiological roles in aging. In bone tissue, higher CypD expression and pore activity are found in aging; however, a causal relationship between CypD/MPTP and bone degeneration needs to be established. We previously reported that CypD expression and MPTP activity are downregulated during osteoblast (OB) differentiation and that manipulations in CypD expression affect OB differentiation and function. Using a newly developed OB-specific CypD/MPTP gain-of-function (GOF) mouse model, we here present evidence that overexpression of a constitutively active K166Q mutant of CypD (caCypD) impairs OB energy metabolism and function, and bone morphological and biomechanical parameters. Specifically, in a spatial-dependent and sex-dependent manner, OB-specific CypD GOF led to a decrease in oxidative phosphorylation (OxPhos) levels, higher oxidative stress, and general metabolic adaptations coincident with the decreased bone organic matrix content in long bones. Interestingly, accelerated bone degeneration was present in vertebral bones regardless of sex. Overall, our work
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- Author
- Rubens Sautchuk; Chen Yu; Matthew McArthur; Christine Massie; Paul S. Brookes; George A. Porter; Hani Awad; Roman A. Eliseev
- Publisher
- Wiley
- Published
- 2023
- Language
- EN
- Field
- Medicine (Health Sciences)