TY - JOUR
T1 - Changes in the intra- and peri-cellular sclerostin distribution in lacuno-canalicular system induced by mechanical unloading
AU - Osumi, Ryuta
AU - Wang, Ziyi
AU - Ishihara, Yoshihito
AU - Odagaki, Naoya
AU - Iimura, Tadahiro
AU - Kamioka, Hiroshi
N1 - Funding Information:
The authors would like to thank Masumi Furutani and Megumi Tsukano, Central Research Laboratory, Okayama University Medical School, for their technical assistance in this study. This work was supported by a Grant-in-Aid for Scientific Research (to T. Iimura [18H02983], Y. Ishihara [17H04413], Z. Wang [19J11906] and H. Kamioka [16H05549, 19H03859]) from the Japan Society for the Promotion of Science, Japan.
Funding Information:
The authors would like to thank Masumi Furutani and Megumi Tsukano, Central Research Laboratory, Okayama University Medical School, for their technical assistance in this study. This work was supported by a Grant-in-Aid for Scientific Research (to T. Iimura [18H02983], Y. Ishihara [17H04413], Z. Wang [19J11906] and H. Kamioka [16H05549, 19H03859]) from the Japan Society for the Promotion of Science, Japan.
Publisher Copyright:
© 2020, The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Lacuno-canalicular system
KW - Mechanical unloading
KW - Sclerostin distribution
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U2 - 10.1007/s00774-020-01135-9
DO - 10.1007/s00774-020-01135-9
M3 - Article
C2 - 32844318
AN - SCOPUS:85089827880
VL - 39
SP - 148
EP - 159
JO - Journal of Bone and Mineral Metabolism
JF - Journal of Bone and Mineral Metabolism
SN - 0914-8779
IS - 2
ER -