title: The impact of bone marrow adipocytes on osteoblast and osteoclast differentiation.
abstract: Throughout life, bone is constantly remodeled through the complementary processes of bone resorption and bone formation. Highly coordinated regulation of these activities is essential for maintaining consistent bone quality and quantity. Normally, the development and function of bone-forming (osteoblast) and bone-resorbing (osteoclast) cells are tightly regulated by signaling molecules secreted by these two cell types. Within the bone marrow microenvironment, osteoblasts arise from mesenchymal stem cells (MSCs), which are in close contact with the hematopoietic stem cell (HSC) precursors that differentiate into mature osteoclasts. Signaling molecules secreted by osteoblasts (e.g., receptor activator of nuclear factor kappa B ligand and osteoprotegerin) and osteoclasts (e.g., bone morphogenetic protein 6, wingless-type MMTV integration site family member 10B, sphingosine-1-phosphate, and ephrin-B2) play a key role in bone remodeling by guiding the differentiation, localization, and function of bone cells. In addition to osteoblasts, bone marrow MSCs can also differentiate into adipocytes that affect bone remodeling by competitively suppressing intracellular osteogenic signals, including runt-related transcription factor 2, osterix, and beta-catenin, while simultaneously promoting the secretion of adipogenic signaling molecules such as leptin, adiponectin, chemerin, omentin-1, resistin, and visfatin. Secreted adipogenic factors have also been shown to affect the osteoclastogenic differentiation of HSCs. Herein, we discuss the impact of bone marrow adipocytes on the coupling of osteoblast and osteoclast differentiation, and the relevance to bone-loss disorders such as osteoporosis. © 2014 IUBMB Life, 66(3):147-155, 2014.
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Muruganandan
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sinal
keywords: adipocyte; bone remodeling; osteoblast; osteoclast; stem cell