PDF(Pubmed)
Abstract：
Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.
摘要：
成骨通过破骨细胞的骨吸收和随后的成骨细胞的骨形成之间的平衡而不断地重塑。许多研究提供了分子证据，表明骨骼重塑是在昼夜节律的控制下。据报道，骨转换标志物的血清和尿液水平有昼夜节律波动，如消化的胶原蛋白片段和骨碱性磷酸酶。此外,超过四分之一的骨骼记录显示昼夜节律，包括编码成骨细胞生成和破骨细胞生成的主转录因子的基因，成骨细胞因子，和信号通路蛋白。血清钙水平,磷酸盐,甲状旁腺激素,降钙素也显示昼夜节律。最后,靶向核心昼夜节律调节基因Bmal1的成骨细胞和破骨细胞特异性敲除小鼠显示破坏的骨重建，尽管结果并不总是一致的。尽管有这些研究,然而,在体内建立昼夜节律和骨骼重塑之间的直接联系仍然是一个主要挑战。在遵循昼夜节律变化的同时重复地从人类受试者收集骨材料几乎是不可能的。此外,昼夜人类和夜间小鼠的昼夜节律基因调控差异，主要的模式生物，仍然不清楚。填补骨骼重塑昼夜节律调节的知识空白可以揭示许多骨骼疾病（包括骨质疏松症）的新调节机制。遗传性疾病,和骨折愈合。对于在周期性波动环境的影响下细胞分化如何进行的基本理解，这也是一个重要问题。
