The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity

Abstract

The number of mature osteoblasts and marrow adipocytes in bone is influenced by the differentiation of the common mesenchymal progenitor cell towards one phenotype and away from the other. Consequently, factors which promote adipogenesis not only lead to fatty marrow but also inhibit osteoblastogenesis, resulting in decreased osteoblast numbers, diminished bone formation and, potentially, inadequate bone mass and osteoporosis. In addition to osteoblast and bone adipocyte numbers being influenced by this skewing of progenitor cell differentiation towards one phenotype, mature osteoblasts and adipocytes secrete factors which may evoke changes in the cell fate and function of each other. This review examines the endogenous factors, such as PPAR-γ2, Wnt, IGF-1, GH, FGF-2, oestrogen, the GP130 signalling cytokines, vitamin D and glucocorticoids, which regulate the selection between osteoblastogenesis and adipogenesis and the interrelationship between fat and bone. The role of adipokines on bone, such as adiponectin and leptin, as well as adipose-derived oestrogen, is reviewed and the role of bone as an energy regulating endocrine organ is discussed.

The Role of Bone Marrow Microenvironment in Governing the Balance between Osteoblastogenesis and Adipogenesis

“…However, clinical investigation demonstrated a positive link between serum leptin levels and bone mineral density (BMD), especially in women. Yet a number of other studies suggested no correlation [114]. Adiponectin is another adipose secreted adipokine with critical roles in glucose metabolism and energy homeostasis [115].…”

Bone Physiology: Bone Cells, Modeling, and Remodeling

“…Freidenstein [ 33 ] coined the terms inducible and determined osteoprogenitor cells (IOPCs and DOPCs) to indicate that there were stromal that were pluripotential and could be induced to form osteoblasts, while other cells further along the differentiation pathway were irreversibly differentiated. This concept was revised because cells that have many of the characteristics of DOPCs can be diverted in culture to other phenotypes such as adipocytes or cartilage cells [ 34 ]. Thus it seems more likely that the process of differentiation is a continuum with many different stages.…”

Bone and adipose tissue – more and more interdependence

“…Studies conducted in the last several years indicate that bone marrow adipocytes have the characteristic features of subcutaneous and visceral fat [1,14]. They are metabolically active as they secrete multiple biologically active substances that affect osteoblastogenesis.…”

“…Thus, what we encounter here is a positive feedback loop: a signal sent by the pancreas via an osteoblast promotes osteocalcin secretion, which in turn stimulates beta cells to produce insulin. One may presume that the process is to compensate energy expenditure related to osteogenesis, and the term "bone-pancreas axis" has been coined as a result [14,48]. The bond of negative regulation that is necessary in every biological process turns out to be leptin.…”