Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.
Department of Molecular Biology, ICMR-NIREH, Bhopal 462030, India.
Cells. 2022 Dec 6;11(23):3943. doi: 10.3390/cells11233943.
Renewing interest in the study of intermediate metabolism and cellular bioenergetics is brought on by the global increase in the prevalence of metabolic illnesses. Understanding of the mechanisms that integrate energy metabolism in the entire organism has significantly improved with the application of contemporary biochemical tools for quantifying the fuel substrate metabolism with cutting-edge mouse genetic procedures. Several unexpected findings in genetically altered mice have prompted research into the direction of intermediate metabolism of skeletal cells. These findings point to the possibility of novel endocrine connections through which bone cells can convey their energy status to other metabolic control centers. Understanding the expanded function of skeleton system has in turn inspired new lines of research aimed at characterizing the energy needs and bioenergetic characteristics of these bone cells. Bone-forming osteoblast and bone-resorbing osteoclast cells require a constant and large supply of energy substrates such as glucose, fatty acids, glutamine, etc., for their differentiation and functional activity. According to latest research, important developmental signaling pathways in bone cells are connected to bioenergetic programs, which may accommodate variations in energy requirements during their life cycle. The present review article provides a unique perspective of the past and present research in the metabolic characteristics of bone cells along with mechanisms governing energy substrate utilization and bioenergetics. In addition, we discussed the therapeutic inventions which are currently being utilized for the treatment and management of bone-related diseases such as osteoporosis, rheumatoid arthritis (RA), osteogenesis imperfecta (OIM), etc., by modulating the energetics of bone cells. We further emphasized on the role of GUT-associated metabolites (GAMs) such as short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), indole derivates, bile acids, etc., in regulating the energetics of bone cells and their plausible role in maintaining bone health. Emphasis is importantly placed on highlighting knowledge gaps in this novel field of skeletal biology, i.e., "Osteometabolism" (proposed by our group) that need to be further explored to characterize the physiological importance of skeletal cell bioenergetics in the context of human health and bone related metabolic diseases.
代谢疾病的全球流行促使人们重新关注中间代谢和细胞生物能量学的研究。通过应用当代生化工具来量化燃料基质代谢，并结合先进的小鼠遗传程序，对整合整个生物体能量代谢的机制的理解有了显著提高。在基因改变的小鼠中发现的一些意外结果促使人们对骨骼细胞中间代谢进行研究。这些发现表明，通过骨骼细胞向其他代谢控制中心传递其能量状态的新的内分泌连接是可能的。对骨骼系统扩展功能的理解反过来又激发了新的研究，旨在描述这些骨骼细胞的能量需求和生物能量特征。成骨细胞和破骨细胞等骨形成细胞和骨吸收细胞需要不断提供大量的能量底物，如葡萄糖、脂肪酸、谷氨酰胺等，以维持其分化和功能活性。根据最新研究，骨细胞中的重要发育信号通路与生物能量程序相连，这可能适应其生命周期中能量需求的变化。本文综述了骨细胞代谢特征的过去和现在的研究，以及能量底物利用和生物能量学的调控机制。此外，我们还讨论了目前通过调节骨骼细胞的能量学来治疗和管理与骨骼相关的疾病（如骨质疏松症、类风湿关节炎（RA）、成骨不全症（OIM）等）的治疗发明。我们进一步强调了肠道相关代谢物（GAMs）如短链脂肪酸（SCFAs）、中链脂肪酸（MCFAs）、吲哚衍生物、胆汁酸等在调节骨骼细胞能量学及其在维持骨骼健康中的可能作用。我们特别强调了突出这个骨骼生物学新领域（即我们小组提出的“骨代谢”）中的知识空白的重要性，需要进一步探索以描述骨骼细胞生物能量学在人类健康和与骨骼相关的代谢疾病中的生理重要性。
