Sakai Akinori
   Department   Wakamatsu Hospital of the University of Occupational and Environmental Health  Hospital President, Wakamatsu Hospital
   School of Medicine  Orthopedic Surgery, Clinical Medical Sciences
Article types journal article
Language English
Peer review Peer reviewed
Title Elcatonin prevents bone loss caused by skeletal unloading by inhibiting preosteoclast fusion through the unloading-induced high expression of calcitonin receptors in bone marrow cells.
Journal Formal name:Bone
ISSN code:18732763/18732763
Domestic / ForeginForegin
Volume, Issue, Page 85,70-80頁
Author and coauthor Tsukamoto Manabu, Menuki Kunitaka, Murai Teppei, Hatakeyama Akihisa, Takada Shinichiro, Furukawa Kayoko, Sakai Akinori
Publication date 2016/04
Summary This study aimed to clarify whether elcatonin (EL) has a preventive action on bone dynamics in skeletal unloading. Seven-week-old male C57BL/6J mice with either ground control (GC) or tail suspension (TS) were administered EL 20U/kg or a vehicle (veh) three times per week and assigned to one of the following four groups: GCEL, GCveh, TSEL, and TSveh. Blood samples and bilateral femurs and tibias of the mice were obtained for analysis. After 7days of unloading, the trabecular bone mineral density in the distal femur obtained via peripheral quantitative computed tomography and the trabecular bone volume were significantly higher in the TSEL group than in the TSveh group. The bone resorption histomorphometric parameters, such as the osteoclast surface and osteoclast number, were significantly suppressed in the TSEL mice, whereas the number of preosteoclasts was significantly increased. The plasma level of tartrate-resistant acid phosphatase-5b (TRACP-5b) was significantly lower in the TSEL group than in all other groups. In the bone marrow cell culture, the number of TRACP-positive (TRACP(+)) multinucleated cells was significantly lower in the TSEL mice than in the TSveh mice, whereas the number of TRACP(+) mononucleated cells was higher in the TSEL mice. On day 4, the expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), cathepsin K and d2 isoform of vacuolar ATPase V0 domain (ATP6V0D2) mRNA in the bone marrow cells in the TSEL mice was suppressed, and the expression of calcitonin receptor (Calcr) mRNA on day 1 and Calcr antigen on day 4 were significantly higher in the TSveh mice than in the GCveh mice. EL prevented the unloading-induced bone loss associated with the high expression of Calcr in the bone marrow cells of mouse hindlimbs after tail suspension, and it suppressed osteoclast development from preosteoclasts to mature osteoclasts through bone-resorbing activity. This study of EL-treated unloaded mice provides the f
DOI 10.1016/j.bone.2016.01.025
PMID 26851124