Abstract
Bone is a complex tissue composing of mineralized bone, bone cells, hematopoietic cells, marrow adipocytes, and supportive stromal cells. The homeostasis of bone and marrow niche is dynamically regulated by nutrients. The positive correlation between cardiovascular disease and osteoporosis risk suggests a close relationship between hyperlipidemia and/or hypercholesterolemia and the bone metabolism. Cholesterol and its metabolites influence the bone homeostasis through modulating the differentiation and activation of osteoblasts and osteoclasts. The effects of cholesterol on hematopoietic stem cells, including proliferation, migration, and differentiation, are also well-documented and further relate to atherosclerotic lesions. Correlation between circulating cholesterol and bone marrow adipocytes remains elusive, which seems opposite to its effects on osteoblasts. Epidemiological evidence has demonstrated that cholesterol deteriorates or benefits bone metabolism depending on the types, such as low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol. In this review, we will summarize the latest progress of how cholesterol regulates bone metabolism and bone marrow microenvironment, including the hematopoiesis and marrow adiposity. Elucidation of these association and factors is of great importance in developing therapeutic options for bone related diseases under hypercholesterolemic conditions.
Highlights
Bone is a rigid organ but plays important roles in our body
Cholesterol treatment reduced the expression of osteoblastic genes, such as alkaline phosphatase (ALP, Alpl), collagen 1 (Col1a1), bone morphogenic protein (BMP2) and runt related transcription factor 2 (Runx2). These findings suggest that free cholesterol may inhibit the BMP2 to block the expression of Runx2, Alpl, and Col1a1 in osteoblast cells, which in turn inhibits osteoblast differentiation
This study shows that exogenous cholesterol inhibits osteoblast differentiation, and physiological levels of endogenous cholesterol are essential for bone marrow stem cell osteogenesis
Summary
Bone is a rigid organ but plays important roles in our body. It provides mechanical support for the soft tissues and enables mobility. Bone and marrow niche are highly innervated and vascularized This seemingly closed system is tightly connected with the whole body metabolic homeostasis and subject to dynamical regulation by hormones and nutrients. Statins are commonly used to lower cholesterol, by competitively inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate pathway They could lower LDL cholesterol and raise HDL cholesterol concentrations [14]. BMAT is gaining more attention due to its close relationship with bone metabolism and hematopoiesis In newborns, all these bones are filled with hematopoietic cells, but at later stages of life, the number of hematopoietic components decreases, and the bone marrow adipocytes increase [17,18,19]. We review the bone tissue as a complex system, which includes bone cells, hematopoietic cells, and marrow adipocytes, and summarize the latest insights about roles of cholesterol in bone and marrow niche homeostasis
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