Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Department of Allied Health Sciences, Chitkara School of Health Sciences, Chitkara University, Chandigarh, Punjab, India.
J Cell Physiol. 2023 Jul;238(7):1431-1464. doi: 10.1002/jcp.31036. Epub 2023 May 14.
Osteoclasts, the bone-resorbing cells, are essential for the bone remodeling process and are involved in the pathophysiology of several bone-related diseases. The extensive corpus of in vitro research and crucial mouse model studies in the 1990s demonstrated the key roles of monocyte/macrophage colony-stimulating factor, receptor activator of nuclear factor kappa B ligand (RANKL) and integrin αvβ3 in osteoclast biology. Our knowledge of the molecular mechanisms by which these variables control osteoclast differentiation and function has significantly advanced in the first decade of this century. Recent developments have revealed a number of novel insights into the fundamental mechanisms governing the differentiation and functional activity of osteoclasts; however, these mechanisms have not yet been adequately documented. Thus, in the present review, we discuss various regulatory factors including local and hormonal factors, innate as well as adaptive immune cells, noncoding RNAs (ncRNAs), etc., in the molecular regulation of the intricate and tightly regulated process of osteoclastogenesis. ncRNAs have a critical role as epigenetic controllers of osteoclast physiologic activities, including differentiation and bone resorption. The primary ncRNAs, which include micro-RNAs, circular RNAs, and long noncoding RNAs, form a complex network that affects gene transcription activities associated with osteoclast biological activity. Greater knowledge of the involvement of ncRNAs in osteoclast biological activities will contribute to the treatment and management of several skeletal diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc. Moreover, we further outline potential therapies targeting these regulatory pathways of osteoclastogenesis in distinct bone pathologies.
破骨细胞是一种骨吸收细胞，对于骨重塑过程至关重要，并且参与了几种与骨相关疾病的病理生理学过程。在 20 世纪 90 年代，大量的体外研究和关键的小鼠模型研究表明，单核细胞/巨噬细胞集落刺激因子、核因子 κB 配体受体激活剂（RANKL）和整合素 αvβ3 在破骨细胞生物学中起着关键作用。在本世纪的第一个十年里，我们对这些变量控制破骨细胞分化和功能的分子机制的认识有了显著的提高。最近的研究进展揭示了许多关于控制破骨细胞分化和功能活性的基本机制的新见解；然而，这些机制尚未得到充分的记录。因此，在本综述中，我们讨论了各种调节因子，包括局部和激素因子、先天和适应性免疫细胞、非编码 RNA（ncRNA）等，在破骨细胞生成这一复杂而严格调控的过程中的分子调控作用。ncRNA 作为破骨细胞生理活动的表观遗传控制器，在破骨细胞的分化和骨吸收中起着关键作用。主要的 ncRNA 包括 micro-RNAs、circRNA 和长链非编码 RNA，它们形成了一个复杂的网络，影响与破骨细胞生物学活性相关的基因转录活动。对 ncRNA 参与破骨细胞生物学活性的认识的加深将有助于治疗和管理几种骨骼疾病，如骨质疏松症、骨关节炎、类风湿关节炎等。此外，我们进一步概述了针对这些破骨细胞生成调节途径的潜在治疗方法，以治疗不同的骨骼疾病。
