Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, 10065, USA.
Semin Immunopathol. 2019 Sep;41(5):565-572. doi: 10.1007/s00281-019-00757-0. Epub 2019 Sep 24.
Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of the bone. Defects in osteoclasts thus result in unbalanced bone remodeling, leading to numerous pathological conditions such as osteoporosis, bone metastasis, and inflammatory bone erosion. Metabolism is any process a cell utilizes to meet its energetic demand for biological functions. Along with signaling pathways and osteoclast-specific gene expression programs, osteoclast differentiation activates metabolic programs. The energy generated from metabolic reprogramming in osteoclasts not only supports the phenotypic changes from mononuclear precursor cells to multinuclear osteoclasts, but also facilitates bone resorption, a major function of terminally differentiated, mature osteoclasts. While oxidative phosphorylation is studied as a major metabolic pathway that fulfills the energy demands of osteoclasts, all metabolic pathways are closely interconnected. Therefore, it remains important to understand the various aspects of osteoclast metabolism, including the roles and effects of glycolysis, glutaminolysis, fatty acid synthesis, and fatty acid oxidation. Targeting the pathways associated with metabolic reprogramming has shown beneficial effects on pathological conditions. As a result, it is clear that a deeper understanding of metabolic regulation in osteoclasts will offer broader translational potential for the treatment of human bone disorders.
破骨细胞是一种骨吸收细胞，在骨重塑中起着至关重要的作用。因此，破骨细胞的缺陷会导致骨重塑失衡，导致许多病理状况，如骨质疏松症、骨转移和炎症性骨侵蚀。代谢是细胞用于满足其生物功能能量需求的任何过程。除了信号通路和破骨细胞特异性基因表达程序外，破骨细胞分化还激活代谢程序。破骨细胞代谢重编程产生的能量不仅支持单核前体细胞向多核破骨细胞的表型变化，而且还促进骨吸收，这是终末分化的成熟破骨细胞的主要功能。虽然氧化磷酸化被研究为满足破骨细胞能量需求的主要代谢途径，但所有代谢途径都密切相关。因此，了解破骨细胞代谢的各个方面仍然很重要，包括糖酵解、谷氨酰胺分解、脂肪酸合成和脂肪酸氧化的作用和影响。针对与代谢重编程相关的途径已显示出对病理状况的有益影响。因此，很明显，深入了解破骨细胞的代谢调节将为治疗人类骨骼疾病提供更广泛的转化潜力。
