Modulation of Bone and Marrow Niche by Cholesterol

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.

Keywords: bone marrow adipocytes; bone metabolism; cholesterol; hematopoiesis.

Figure 1

Summary of the effects of cholesterol on bone and marrow niche homeostasis. In the circulation, cholesterol is present in the forms of high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) with lipoproteins. Normal concentrations of cholesterol are essential for the body. However, when the circulating concentration changes, it may become a risk factor. This review focuses on the roles of cholesterol in bone metabolism and bone marrow nice homeostasis. Cholesterol could drive the differentiation of marrow stromal cells (MSCs) into either osteoblasts or bone marrow adipocytes (BMAs), and further influence the bone mass or osteoporosis. Meanwhile, cholesterol affects the proliferation and mobilization of hematopoietic stem cells (HSCs), myeloid lineage differentiation and thrombocytosis, effects of which may potentially contribute to the development of atherothrombosis.