glycogen and Osteogenesis-Imperfecta

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that most often arises from type I collagen-COL1A1 and COL1A2-gene defects leading to skeletal fragility, short stature, blue-gray sclera, and muscle weakness. Relative to the skeletal fragility, muscle weakness is much less understood. Recent investigations into OI muscle weakness in both patients and mouse models have revealed the presence of an inherent muscle pathology. Understanding the mechanisms responsible for OI muscle weakness is critical, particularly in light of the extensive cross-talk between muscle and bone via mechanotransduction and biochemical signaling. In the following study we initially subjected WT and oim/oim mice, modeling severe human OI type III, to either weight-bearing (voluntary wheel-running) or non-weight-bearing (swimming) exercise regimens as a modality to improve muscle strength and ultimately bone strength. The oim/oim mice ran only 35% to 42% of the distance run by age- and sex-matched WT mice and exhibited little improvement with either exercise regimen. Upon further investigation, we determined that oim/oim gastrocnemius muscle exhibited severe mitochondrial dysfunction as characterized by a 52% to 65% decrease in mitochondrial respiration rates, alterations in markers of mitochondrial biogenesis, mitophagy, and the electron transport chain components, as well as decreased mitochondrial citrate synthase activity, relative to age- and sex-matched WT gastrocnemius muscle. Thus, mitochondrial dysfunction in the oim/oim mouse likely contributes to compromised muscle function and reduced physical activity levels. © 2019 American Society for Bone and Mineral Research.

Topics: Animals; Biomarkers; Bone and Bones; Disease Models, Animal; DNA, Mitochondrial; Electron Transport; Female; Glycogen; Male; Membrane Proteins; Mice, Inbred C57BL; Microtubule-Associated Proteins; Mitochondria; Mitochondrial Proteins; Mitophagy; Muscles; Organ Size; Organelle Biogenesis; Osteogenesis Imperfecta; Physical Conditioning, Animal; Swimming

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Bone Matrix; Bone Resorption; Calcium Phosphates; Child; Glycogen; Golgi Apparatus; Histocytochemistry; Humans; Ilium; Microscopy, Electron; Osteoblasts; Osteogenesis; Osteogenesis Imperfecta