Osumi, Ryuta Department of Orthodontics, Okayama University Hospital
Wang, Ziyi Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ishihara, Yoshihito Department of Orthodontics, Okayama University Hospital ORCID Kaken ID publons researchmap
Odagaki, Naoya Department of Orthodontics, Okayama University Hospital
Iimura, Tadahiro Department of Pharmacology, Graduate School of Dental Medicine, Hokkaido University
Introduction Mechanical stimuli regulate Sclerostin (Scl), a negative regulator of bone formation, expression in osteocytes. However, the detailed Scl distribution in osteocytes in response to mechanical unloading remains unclear. Materials and methods Twelve-week-old male rats were used. The sciatic and femoral nerves on the right side were excised as mechanical unloading treatment. A sham operation was performed on the left side. One week after neurotrauma, the bone density of the femora was evaluated by peripheral quantitative computed tomography, and immunofluorescence was performed in coronal sections of the femoral diaphysis. The mean fluorescence intensity and fluorescent profile of Scl from the marrow to the periosteal side were analyzed to estimate the Scl expression and determine to which side (marrow or periosteal) the Scl prefers to distribute in response to mechanical unloading. The most sensitive region indicated by the immunofluorescence results was further investigated by transmission electron microscopy (TEM) with immunogold staining to show the Scl expression changes in different subcellular structures. Results In femur distal metaphysis, neurotrauma-induced mechanical unloading significantly decreased the bone density, made the distribution of Scl closer to the marrow on the anterior and medial side, and increased the Scl expression only on the lateral side. TEM findings showed that only the expression of Scl in canaliculi was increased by mechanical unloading. Conclusions Our results showed that even short-term mechanical unloading is enough to decrease bone density, and mechanical unloading not only regulated the Scl expression but also changed the Scl distribution in both the osteocyte network and subcellular structures.
This fulltext is available in Aug. 2021.
Journal of Bone and Mineral Metabolism
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Japan Society for the Promotion of Science