PMID- 34418462 OWN - NLM STAT- MEDLINE DCOM- 20220328 LR - 20220328 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 176 DP - 2021 Nov TI - Calcitonin gene-related peptide and brain-derived serotonin are related to bone loss in ovariectomized rats. PG - 85-92 LID - S0361-9230(21)00255-0 [pii] LID - 10.1016/j.brainresbull.2021.08.007 [doi] AB - OBJECTIVES: Postmenopausal osteoporosis (PMO) and osteoporotic fracture seriously impair human health in developed countries. The present study aims to explore whether sensory nerves, calcitonin gene-related peptide (CGRP), and brain-derived serotonin are related to bone loss in ovariectomized (OVX) rats. METHODS: Female rats were grouped into the ovariectomized (OVX) and sham surgery (SHAM) groups. Immunocytochemistry, western blotting, and qPCR were performed to detect CGRP expression in the femurs. The expression levels of serotonin and CGRP in the spinal cord and brainstem were estimated using western blotting, immunofluorescence, and qPCR. ELISA was used to evaluate the serum biomarkers of bone formation and resorption. Bone mineral density was measured using dual-energy X-ray (DXA) analysis. Femur microstructure was imaged by Micro CT. P values less than 0.05 were considered statistically significant. RESULTS: ELISA showed that serum bone alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), beta-crosslaps, and beta-ctx were increased in the OVX group. In the OVX group, in vivo bone mineral density, trabecular bone mineral density, bone volume fraction (BV/TV), and trabecular number (Tb. N) were significantly decreased, while trabecular spacing (Tb. Sp) and trabecular bone pattern factor (Tb. Pf) were markedly increased. In the OVX group, the expression levels of CGRP of the femur were significantly downregulated. In contrast, CGRP and serotonin expression was increased in the spinal cord of the OVX group. Serotonin expression was increased in the brainstem, brainstem nucleus raphe magnus (RMG), and nucleus raphe dorsalis (DRN). CONCLUSION: Our results indicated that the activation of osteoclast triggered the release of CGRP from nociceptive sensory nerve fibers and transmitted this painful stimulus to the dorsal horn of the spinal cord to release increased CGRP. The descending serotonergic inhibitory system was activated by increased CGRP levels of the spinal cord and promoted serotonin release in the brainstem RMG, DRN, and the spinal cord, contributing to the decreased CGRP level in bone tissue, which revealed a novel mechanism of bone loss in PMO. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Zhang, Rui-Hao AU - Zhang RH AD - Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu, 730000, PR China; Key Laboratory of Bone and Joint Disease Research of Gansu Province, Lanzhou, 730000, PR China. FAU - Zhang, Xiao-Bo AU - Zhang XB AD - Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu, 730000, PR China; Key Laboratory of Bone and Joint Disease Research of Gansu Province, Lanzhou, 730000, PR China. FAU - Lu, Yu-Bao AU - Lu YB AD - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, PR China. FAU - Hu, Yi-Cun AU - Hu YC AD - Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu, 730000, PR China; Key Laboratory of Bone and Joint Disease Research of Gansu Province, Lanzhou, 730000, PR China. FAU - Chen, Xiang-Yi AU - Chen XY AD - Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu, 730000, PR China; Key Laboratory of Bone and Joint Disease Research of Gansu Province, Lanzhou, 730000, PR China. FAU - Yu, De-Chen AU - Yu DC AD - Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu, 730000, PR China; Key Laboratory of Bone and Joint Disease Research of Gansu Province, Lanzhou, 730000, PR China. FAU - Shi, Jin-Tao AU - Shi JT AD - Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu, 730000, PR China; Key Laboratory of Bone and Joint Disease Research of Gansu Province, Lanzhou, 730000, PR China. FAU - Yuan, Wen-Huan AU - Yuan WH AD - Baotou First Affiliated Hospital of Inner Mongolia University of Science and Technology, Baotou, 014000, PR China. FAU - Wang, Jing AU - Wang J AD - The People's Hospital of Baoan District, Shenzhen, 518000, PR China. Electronic address: wangjing1mail@163.com. FAU - Zhou, Hai-Yu AU - Zhou HY AD - Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, Gansu, 730000, PR China; Lanzhou Xigu District People's Hospital, Lanzhou, Gansu, 730000, PR China. Electronic address: zhouhy@lzu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210818 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 333DO1RDJY (Serotonin) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) SB - IM MH - Absorptiometry, Photon MH - Alkaline Phosphatase/blood MH - Animals MH - Bone Density/*physiology MH - Bone and Bones/diagnostic imaging MH - Brain Stem/metabolism MH - Calcitonin Gene-Related Peptide/*metabolism MH - Female MH - Osteoporosis/diagnostic imaging/*metabolism MH - Ovariectomy MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/*metabolism MH - Spinal Cord/metabolism MH - Tartrate-Resistant Acid Phosphatase/blood OTO - NOTNLM OT - Bone microstructure OT - Calcitonin gene-related peptide OT - Osteoporosis OT - Serotonin EDAT- 2021/08/22 06:00 MHDA- 2022/03/29 06:00 CRDT- 2021/08/21 20:13 PHST- 2021/05/03 00:00 [received] PHST- 2021/08/05 00:00 [revised] PHST- 2021/08/16 00:00 [accepted] PHST- 2021/08/22 06:00 [pubmed] PHST- 2022/03/29 06:00 [medline] PHST- 2021/08/21 20:13 [entrez] AID - S0361-9230(21)00255-0 [pii] AID - 10.1016/j.brainresbull.2021.08.007 [doi] PST - ppublish SO - Brain Res Bull. 2021 Nov;176:85-92. doi: 10.1016/j.brainresbull.2021.08.007. Epub 2021 Aug 18.