Abstract
Osteoporosis (OP) is a systemic bone disease characterized by decreased bone strength, microarchitectural changes in bone tissues, and increased risk of fracture. Its occurrence is closely related to various factors such as aging, genetic factors, living habits, and nutritional deficiencies as well as the disturbance of bone homeostasis. The dysregulation of bone metabolism is regarded as one of the key influencing factors causing OP. Cholesterol oxidation products (COPs) are important compounds in the maintenance of bone metabolic homeostasis by participating in several important biological processes such as the differentiation of mesenchymal stem cells, bone formation in osteoblasts, and bone resorption in osteoclasts. The effects of specific COPs on mesenchymal stem cells are mainly manifested by promoting osteoblast genesis and inhibiting adipocyte genesis. This review aims to elucidate the biological roles of COPs in OP development, starting from the molecular mechanisms of OP, pointing out opportunities and challenges in current research, and providing new ideas and perspectives for further studies of OP pathogenesis.
Highlights
Osteoporosis (OP) is a multifactorial degenerative disease characterized by decreased bone mass, reduced bone mineral density (BMD), and increased risk of fracture [1]
Previous studies have shown that along with aging, both calcium loss and hormone metabolism disorders result in disruption of lipid metabolism, which leads to disturbance of bone homeostasis and consequent OP [7]
Cholesterol oxidation products (COPs) metabolism in humans can be divided into two main metabolic pathways; one is to produce highly polar water-soluble products that are excreted through the metabolic cycle [57,68]
Summary
Osteoporosis (OP) is a multifactorial degenerative disease characterized by decreased bone mass, reduced bone mineral density (BMD), and increased risk of fracture [1]. Cholesterol oxidation products (COPs) are a class of lipid oxidation products produced through enzymatic or non-enzymatic mechanism from 27-carbon cholesterol, obtained from diet and cholesterol metabolism They are biosynthetic intermediates of bile acids, steroid hormones, and 1,25-dihydroxyvitamin D, which are usually present in the circulation of human and animal tissues in either free or bound states [8,9,10,11]. The COP contents in the human body are extremely low at picogram to nanogram level, they are reported to play important roles in the regulation of human metabolic homeostasis. We have discussed the novel functions of COPs involved in OP pathogenesis that are underexplored so far as follows: (1) molecular mechanisms of OP; (2) anabolism of COPs; (3) regulatory roles of COPs in OP; and (4) challenges
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