Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women
| Autor: | Hong-Wen Deng, Xia-Fang Wang, Rui Gong, Jun-Min Lu, Feng-Ye Lyu, Qiang Zhang, Yin-Hua Zhang, Zhang-Fang Li, Jie Shen, Xu Lin, Qi Zhao, Marco Brotto, Yating Du, Yuan-Cheng Chen, Zhi Chen, Chenglin Mo, Yu-Qian Song, Dao-Yan Pan, Hong-Mei Xiao, Martin R. Schiller, Cheng Peng, Hui Shen, Qing Tian, Hui-Min Liu, Christopher J. Papasian, Kuan-Jui Su, Rou Zhou, Zeng-Xin Ao, Chan-Yan Weng, Shi-di Hu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Adult medicine.medical_specialty China Endocrinology Diabetes and Metabolism Metabolite Clinical Biochemistry Context (language use) Biology Biochemistry Bone remodeling Cell Line chemistry.chemical_compound Mice Endocrinology Metabolomics Absorptiometry Photon Osteoclast Bone Density Osteogenesis Internal medicine medicine Animals Humans Clinical Research Articles Osteoporosis Postmenopausal Bone mineral Biochemistry (medical) Lauric Acids Osteoblast Middle Aged Postmenopause medicine.anatomical_structure Cross-Sectional Studies chemistry Ovariectomized rat Metabolome Female Biomarkers |
| Zdroj: | J Clin Endocrinol Metab |
| Popis: | Context Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. Objective We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. Design and Methods We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. Results Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM). Conclusions This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD. |
| Databáze: | OpenAIRE |
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