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

Biomolecules

JerahmeR. Martinez¹  X.Lucas Lu¹  Ashutosh Parajuli¹  Liyun Wang¹  Shaopeng Pei¹  CatherineB. Kirn-Safran²  MaryC. Farach-Carson³  X.Sherry Liu⁴  Hongbo Zhao⁴ 

[1] Center for Biomechanical Engineering Research, Department of Mechanical Engineering, University of Delaware, Newark, DE 19716, USA;Department of Biology, Widener University, Chester, PA 19013, USA;Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center, Houston, TX 77054, USA;McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;

关键词: perlecan;    schwartz-jampel syndrome;    trabecular bone;    osteoporosis;    osteoclastogenesis;    hindlimb suspension;    re-ambulation;    micro-computed tomography;   

DOI  :  10.3390/biom10020198

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown