Dual Effects of Lipid Metabolism on Osteoblast Function

Abstract

The skeleton is a dynamic and metabolically active organ with the capacity to influence whole body metabolism. This newly recognized function has propagated interest in the connection between bone health and metabolic dysfunction. Osteoblasts, the specialized mesenchymal cells responsible for the production of bone matrix and mineralization, rely on multiple fuel sources. The utilization of glucose by osteoblasts has long been a focus of research, however, lipids and their derivatives, are increasingly recognized as a vital energy source. Osteoblasts possess the necessary receptors and catabolic enzymes for internalization and utilization of circulating lipids. Disruption of these processes can impair osteoblast function, resulting in skeletal deficits while simultaneously altering whole body lipid homeostasis. This article provides an overview of the metabolism of postprandial and stored lipids and the osteoblast's ability to acquire and utilize these molecules. We focus on the requirement for fatty acid oxidation and the pathways regulating this function as well as the negative impact of dyslipidemia on the osteoblast and skeletal health. These findings provide key insights into the nuances of lipid metabolism in influencing skeletal homeostasis which are critical to appreciate the extent of the osteoblast's role in metabolic homeostasis.

The role of statins in the differentiation and function of bone cells

“…In addition, lipids and their derivatives can activated osteoblasts via selective lipid receptors and catabolic enzymes for the internalization and utilization of circulating lipids. Dyslipidaemia and lipid homeostasis disruption can impair osteoblast function and accelerate osteoclast activity 5,6 . Targeting lipid metabolism with a statin has been shown to improve bone density and quality in metabolic bone diseases 7 …”

Comparative Proteomic and Metabolomic Analysis of Human Osteoblasts, Differentiated from Dental Pulp Stem Cells, Hinted Crucial Signaling Pathways Promoting Osteogenesis

“…Histological studies indicated that both mature osteoblasts and differentiating osteoblast progenitors contain stored lipids. Moreover, in vivo and in vitro studies showed that osteoblasts uptake circulating lipoproteins and free fatty acids [ 95 ].…”

“…Particularly, proteins participating in energy production, ACSL3 and ACLS4 (2.17, 2.03-fold increase, respectively) as members of β-oxidation, ATP5MG (2.11-fold increase) responsible for ATP synthesis in mitochondria, NDUFS1, NDUFS3, NDUFV2, and NDUFAF2 (1.02, 1.01, 1.1, 2.97-fold increase, respectively) involved in electron transport chain in mitochondria, SDHA and SDHB (1.13, 1.47-fold increase, respectively) enzymes of TCA cycle. Bone remodeling is an energy-consuming process due to the synthesis of extracellular matrix proteins and the accumulation of mineral ions for hydroxyapatite crystal formation [ 95 ]. Interestingly, the authors reported that insulin signaling affected both bone metabolism and energy production [ 59 ].…”

Abnormal Lipid Profile in Fast-Growing Broilers With Spontaneous Femoral Head Necrosis

“…Bone is a dynamic endocrine organ that regulates its own and even the whole body’s steady-state balance ( Alekos et al, 2020 ). Bone modeling and remodeling are strictly controlled by many factors, including lipids.…”

“…Among the bone components, chicken cortical bone contains a higher fatty acid content than cancellous bone, which allows the intensity of metabolic activity to be maintained ( Dolegowska et al, 2006 ; Liu et al, 2021 ). In addition, the utilization of fatty acids in bone is comparable to that in tissues with more a classic fatty acid metabolism ( Alekos et al, 2020 ). Increasing evidence shows that there is a close correlation between bone fat and many bone diseases ( Bermeo et al, 2014 ).…”