Lu Darlene, Demissie Serkalem, Horowitz Nina B, Gower Adam C, Lenburg Marc E, Alekseyev Yuriy O, Hussein Amira I, Bragdon Beth, Liu Yu, Daukss Dana, Page Jack M, Webster Micheal Z, Schlezinger Jennifer J, Morgan Elise F, Gerstenfeld Louis C
Department of Biostatistics Boston University School of Public Health Boston MA USA.
Department of Orthopaedic Surgery Boston University School of Medicine Boston MA USA.
JBMR Plus. 2021 Dec 10;6(2):e10579. doi: 10.1002/jbm4.10579. eCollection 2022 Feb.
Time is a central element of the sexual dimorphic patterns of development, pathology, and aging of the skeleton. Because the transcriptome is a representation of the phenome, we hypothesized that both sex and sex-specific temporal, transcriptomic differences in bone tissues over an 18-month period would be informative to the underlying molecular processes that lead to postnatal sexual dimorphism. Regardless of age, sex-associated changes of the whole bone transcriptomes were primarily associated not only with bone but also vascular and connective tissue ontologies. A pattern-based approach used to screen the entire Gene Expression Omnibus (GEO) database against those that were sex-specific in bone identified two coordinately regulated gene sets: one related to high phosphate-induced aortic calcification and one induced by mechanical stimulation in bone. Temporal clustering of the transcriptome identified two skeletal tissue-associated, sex-specific patterns of gene expression. One set of genes, associated with skeletal patterning and morphology, showed peak expression earlier in females. The second set of genes, associated with coupled remodeling, had quantitatively higher expression in females and exhibited a broad peak between 3 to 12 months, concurrent with the animals' reproductive period. Results of phenome-level structural assessments of the tibia and vertebrae, and in vivo and in vitro analysis of cells having osteogenic potential, were consistent with the existence of functionally unique, skeletogenic cell populations that are separately responsible for appositional growth and intramedullary functions. These data suggest that skeletal sexual dimorphism arises through sex-specific, temporally different processes controlling morphometric growth and later coupled remodeling of the skeleton during the reproductive period of the animal. © 2021 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
时间是骨骼发育、病理和衰老的性别二态性模式的核心要素。由于转录组是表型组的一种体现，我们推测，在18个月的时间里，骨组织中性别特异性的时间转录组差异对于导致出生后性别二态性的潜在分子过程具有重要意义。无论年龄如何，全骨转录组的性别相关变化不仅主要与骨骼有关，还与血管和结缔组织本体相关。一种基于模式的方法用于筛选整个基因表达综合数据库（GEO）中与骨骼性别特异性相关的数据库，该方法确定了两个协同调控的基因集：一个与高磷诱导的主动脉钙化有关，另一个由骨骼中的机械刺激诱导。转录组的时间聚类确定了两种与骨骼组织相关的、性别特异性的基因表达模式。一组与骨骼模式和形态相关的基因在雌性中表达峰值出现得更早。第二组与耦合重塑相关的基因在雌性中表达量更高，并且在3至12个月之间呈现出一个宽泛的峰值，这与动物的繁殖期同时出现。胫骨和椎骨的表型水平结构评估结果，以及对具有成骨潜力的细胞进行的体内和体外分析结果，与存在功能独特的成骨细胞群体一致，这些细胞群体分别负责骨的表面生长和骨髓内功能。这些数据表明，骨骼性别二态性是通过性别特异性的、时间上不同的过程产生的，这些过程控制着动物繁殖期骨骼的形态计量生长和随后的耦合重塑。© 2021作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
