Trabecular Bone Deficit and Enhanced Anabolic Response to Re-Ambulation after Disuse in Perlecan-Deficient Skeleton.

摘要: Perlecan/Hspg2, a large monomeric heparan sulfate proteoglycan, is found in the basement membrane and extracellular matrix, where it acts as matrix scaffold, growth factor depot, tissue barrier. Perlecan deficiency leads to skeletal dysplasia Schwartz-Jampel Syndrome (SJS) risk for osteoporosis. In SJS-mimicking murine model (Hypo), inferior cortical bone quality impaired mechanotransduction osteocytes were reported. This study focused on trabecular bone, perlecan was hypothesized result structural deficit altered response disuse re-loading. We compared Hypo versus WT both axial appendicular skeletons of 8-38-week-old male mice, observed severe approximately 50% reduction Tb.BV/TV regardless site animal age. Defects endochondral ossification (e.g., accelerated mineralization), increases osteoclast activity, differentiation progenitor cells marrow contributed phenotype. The deteriorated further under three-week hindlimb suspension did WT. Re-ambulation partially recovered lost Hypo, but not mice. novel finding that low-impact loading could counter detrimental effects perlecan-deficient skeleton suggests strategy maintain health SJS patients.