Defining osteoblast and adipocyte lineages in the bone marrow

Abstract

Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood. With age, the commitment of BMSCs to osteogenesis slows, bone formation decreases, fracture risk rises, and marrow adiposity increases. An unresolved question is whether osteogenesis and adipogenesis are co-regulated in the bone marrow. Osteogenesis and adipogenesis are controlled by specific signaling mechanisms, circulating cytokines, and transcription factors such as Runx2 and Pparγ, respectively. One hypothesis is that adipogenesis is the default pathway if osteogenic stimuli are absent. However, recent work revealed that Runx2 and Osx1-expressing preosteoblasts form lipid droplets under pathological and aging conditions. Histone deacetylase 3 (Hdac3) and other epigenetic regulators suppress lipid storage in preosteoblasts and/or control marrow adiposity. Establishing a better understanding of fat storage in bone marrow cells, as well as the osteoblast-adipocyte relationship within the bone marrow niche is necessary to understand the mechanisms underlying disease- and aging-related marrow fat storage and may lead to the development of new therapeutic targets for "fatty bone" and osteoporosis.

Developmental Exposure to the Flame Retardant Mixture Firemaster 550 Compromises Adult Bone Integrity in Male but not Female Rats

“…This phenomenon, in combination with significantly elevated body weight and left ventricle thickness observed in a prior, similar, study [6], suggests that overall metabolic health may be impaired. These data are consistent with numerous in vitro studies suggesting that FM 550, its components, and structurally related FRs, heighten adiposity at the expense of bone formation [10,[31][32][33][34][35][36][37][38][39][40][41][42][43].…”

“…Bone marrow mesenchymal stem/stromal cells (BMSCs) have multipotential to differentiate into osteoblasts, adipocytes, chondrocytes or myoblasts. Molecular factors and differing signaling pathways controlling transcription may alternatively trigger events that direct BMSCs to osteogenesis or adipogenesis [34]. In cases where BMSCs are not directed towards osteogenesis, bone formation may be impaired resulting in deficient bone microarchitecture.…”

Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway

“…Furthermore, we found that Macf1 f/f Osx-Cre without rhBMP2 treatment that osteoblasts and adipocytes in bone marrow share a common progenitor, and the dynamic balance between them can influence the density and function of bone. 35 In this study, histological staining of Macf1 deficiency femur displayed an increased accumulation of adipocyte ghosts in situ ( Figure 3E). This phenotype is similar to the observations following the β-catenin and Cbfβ deletion in Osx-expressing cells.…”

Cellular senescence mediates the detrimental effect of prenatal dexamethasone exposure on postnatal long bone growth in mice offspring

“…This local environment plays important role in regulating stem cell survival, function and fate [18], and alterations of the microenvironment may impair skeletal stem cells functions, leading to decreased osteogenesis and bone formation [19][20][21].…”