Naqvi Syeda Masooma, O'Sullivan Laura M, Allison Hollie, Casey Vincent J, Schiavi-Tritz Jessica, McNamara Laoise M
Mechanobiology and Medical Devices Research Group (MMDRG), Biomedical Engineering, School of Engineering, College of Science and Engineering, University of Galway, Galway, H91 HX31, Ireland.
University of Lorraine, CNRS, LRGP, F-54000 Nancy, France.
JBMR Plus. 2024 Jul 24;8(9):ziae098. doi: 10.1093/jbmrpl/ziae098. eCollection 2024 Sep.
Osteoporosis is primarily associated with bone loss, but changes in bone tissue matrix composition and osteocyte mechanotransduction have also been identified. However, the molecular mechanisms underlying these changes and their relation to bone loss are not fully understood. The objectives of this study were to (1) conduct comprehensive temporal gene expression analyses on cortical bone tissue from ovariectomized rats, with a specific focus on genes known to govern matrix degradation, matrix production, and mechanotransduction, and (2) correlate these findings with bone mass, trabecular and cortical microarchitecture, and mineral and matrix composition. Microarray data revealed 35 differentially expressed genes in the cortical bone tissue of the ovariectomized cohort. We report that catabolic gene expression abates after the initial accelerated bone loss period, which occurs within the first 4 wk of estrogen deficiency. However, in long-term estrogen deficiency, we report increased expression of genes associated with extracellular matrix deposition (Spp1, COL1A1, COL1A2, OCN) and mechanotransduction (Cx43) compared with age-matched controls and short-term estrogen deficiency. These changes coincided with increased heterogeneity of mineral-to-matrix ratio and collagen maturity, to which extracellular matrix markers COL1A1 and COL1A2 were positively correlated. Interestingly, mineral heterogeneity and collagen maturity, exhibited a negative correlation with PHEX and IFT88, associated with mechanosensory cilia formation and Hedgehog (Hh) signaling. This study provides the first insight into the underlying mechanisms governing secondary mineralization and heterogeneity of matrix composition of bone tissue in long-term estrogen deficiency. We propose that altered mechanobiological responses in long-term estrogen deficiency may play a role in these changes.
骨质疏松症主要与骨质流失有关，但骨组织基质成分的变化和骨细胞机械转导也已被发现。然而，这些变化背后的分子机制及其与骨质流失的关系尚未完全明确。本研究的目的是：（1）对去卵巢大鼠的皮质骨组织进行全面的时间基因表达分析，特别关注已知调控基质降解、基质生成和机械转导的基因；（2）将这些发现与骨量、小梁和皮质微结构以及矿物质和基质成分相关联。微阵列数据显示，去卵巢组的皮质骨组织中有35个差异表达基因。我们报告称，分解代谢基因表达在雌激素缺乏的最初4周内出现的初始加速骨质流失期后减弱。然而，在长期雌激素缺乏的情况下，与年龄匹配的对照组和短期雌激素缺乏相比，我们发现与细胞外基质沉积（Spp1、COL1A1、COL1A2、OCN）和机械转导（Cx43）相关的基因表达增加。这些变化与矿物质与基质比率的异质性增加和胶原蛋白成熟度增加同时出现，细胞外基质标记物COL1A1和COL1A2与它们呈正相关。有趣的是，矿物质异质性和胶原蛋白成熟度与PHEX和IFT88呈负相关，PHEX和IFT88与机械感觉纤毛形成和刺猬（Hh）信号通路有关。本研究首次深入探讨了长期雌激素缺乏情况下骨组织继发性矿化和基质成分异质性的潜在机制。我们认为，长期雌激素缺乏情况下机械生物学反应的改变可能在这些变化中起作用。
