Welhaven Hope D, Vahidi Ghazal, Walk Seth T, Bothner Brian, Martin Stephen A, Heveran Chelsea M, June Ronald K
Department of Chemistry and Biochemistry Montana State University Bozeman MT USA.
Molecular Biosciences Program Montana State University Bozeman MT USA.
JBMR Plus. 2022 Jun 22;6(7):e10654. doi: 10.1002/jbm4.10654. eCollection 2022 Jul.
Cortical bone quality, which is sexually dimorphic, depends on bone turnover and therefore on the activities of remodeling bone cells. However, sex differences in cortical bone metabolism are not yet defined. Adding to the uncertainty about cortical bone metabolism, the metabolomes of whole bone, isolated cortical bone without marrow, and bone marrow have not been compared. We hypothesized that the metabolome of isolated cortical bone would be distinct from that of bone marrow and would reveal sex differences. Metabolite profiles from liquid chromatography-mass spectrometry (LC-MS) of whole bone, isolated cortical bone, and bone marrow were generated from humeri from 20-week-old female C57Bl/6J mice. The cortical bone metabolomes were then compared for 20-week-old female and male C57Bl/6J mice. Femurs from male and female mice were evaluated for flexural material properties and were then categorized into bone strength groups. The metabolome of isolated cortical bone was distinct from both whole bone and bone marrow. We also found sex differences in the isolated cortical bone metabolome. Based on metabolite pathway analysis, females had higher lipid metabolism, and males had higher amino acid metabolism. High-strength bones, regardless of sex, had greater tryptophan and purine metabolism. For males, high-strength bones had upregulated nucleotide metabolism, whereas lower-strength bones had greater pentose phosphate pathway metabolism. Because the higher-strength groups (females compared with males, high-strength males compared with lower-strength males) had higher serum type I collagen cross-linked C-telopeptide (CTX1)/procollagen type 1 N propeptide (P1NP), we estimate that the metabolomic signature of bone strength in our study at least partially reflects differences in bone turnover. These data provide novel insight into bone bioenergetics and the sexual dimorphic nature of bone material properties in C57Bl/6 mice. © 2022 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
具有性别差异的皮质骨质量取决于骨转换，因此取决于重塑骨细胞的活性。然而，皮质骨代谢中的性别差异尚未明确。除了皮质骨代谢存在不确定性外，全骨、无骨髓的分离皮质骨和骨髓的代谢组也未进行比较。我们假设，分离的皮质骨代谢组将不同于骨髓代谢组，并会揭示性别差异。通过液相色谱-质谱联用（LC-MS）生成了20周龄雌性C57Bl/6J小鼠肱骨的全骨、分离皮质骨和骨髓的代谢物谱。然后比较了20周龄雌性和雄性C57Bl/6J小鼠的皮质骨代谢组。对雄性和雌性小鼠的股骨进行弯曲材料特性评估，然后将其分为骨强度组。分离的皮质骨代谢组不同于全骨和骨髓代谢组。我们还在分离的皮质骨代谢组中发现了性别差异。基于代谢物途径分析，雌性具有更高的脂质代谢，而雄性具有更高的氨基酸代谢。无论性别如何，高强度骨具有更强的色氨酸和嘌呤代谢。对于雄性，高强度骨的核苷酸代谢上调，而低强度骨具有更强的磷酸戊糖途径代谢。由于高强度组（雌性与雄性相比，高强度雄性与低强度雄性相比）具有更高的血清I型胶原交联C末端肽（CTX1）/I型前胶原N端前肽（P1NP），我们估计本研究中骨强度的代谢组学特征至少部分反映了骨转换的差异。这些数据为C57Bl/6小鼠的骨生物能量学和骨材料特性的性别差异提供了新的见解。© 2022作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
