Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes.

Evidence indicates that the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells (MSCs) is regulated by several hormones, growth factors, and their downstream signaling cascades. Previous studies suggest that retinoic acid (RA) plays a role in osteoblastogenesis and adipogenesis. However, it is unknown whether RA regulates commitment of MSCs into osteoblasts and adipocytes.

BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation.

Osterix/Sp7, a member of the Sp1 transcription factor family, plays an essential role in bone formation and osteoblastogenesis. Although Osterix has been shown to be induced by BMP2 in a mesenchymal cell line, the molecular basis of the regulation, expression and function of Osterix during osteoblast differentiation, is not fully understood. Thus we examined the role of BMP2 signaling in the regulation of Osterix using the mesenchymal cell lines C3H10T1/2 and C2C12.

MSX2 stimulates chondrocyte maturation by controlling Ihh expression.

Several studies indicated that a homeobox gene, Msx2, is implicated in regulation of skeletal development by controlling enchondral ossification as well as membranous ossification. However, the molecular basis by which Msx2 conducts chondrogenesis is currently unclear. In this study, we examined the role of Msx2 in chondrocyte differentiation using mouse primary chondrocytes and embryonic metatarsal explants.

[Roles of PPAR family in bone metabolisms].

Bone is a complex tissue which contains osteoclasts, osteoblasts, chondrocytes, adipocytes, hematopoietic cells and immune cells. Since osteoblasts share the same origin with adipocytes in bone marrow cavity, it is assumed that PPAR (peroxisome proliferator-activated receptor) family, which is an important nuclear receptor family for adipocyte differentiation, plays a role in the bone microenvironment. Indeed, recent evidences support the primitive roles of PPAR family in osteoblast differentiation as well as adipocyte differentiation.

A CCAAT/enhancer binding protein beta isoform, liver-enriched inhibitory protein, regulates commitment of osteoblasts and adipocytes.

Although both osteoblasts and adipocytes have a common origin, i.e., mesenchymal cells, the molecular mechanisms that define the direction of two different lineages are presently unknown.

Reciprocal roles of MSX2 in regulation of osteoblast and adipocyte differentiation.

Mice deficient in the Msx2 gene manifest defects in skull ossification and a marked reduction in bone formation associated with decreases in osteoblast numbers, thus suggesting that Msx2 is involved in bone formation. However, the precise role of Msx2 during osteoblast differentiation is not fully understood. In the present study, we investigated the role of Msx2 in the regulation of osteoblast differentiation in the multipotent mesenchymal cell lines C3H10T1/2 and C2C12 and in murine primary osteoblasts.

The role of Smads in BMP signaling.

Bone morphogenetic proteins, BMPs, are members of the transforming growth factor-beta (TGF-beta) superfamily, which are implicated in embryogenesis, organogenesis, skeletogenesis, osteogenesis, cellular differentiation and apoptosis by regulating the expression of specific target genes. Recent progresses in studying the BMP signaling reveal that a cytoplasmic protein family, Smad, plays a central role in mediating the biological effects of BMPs. Smad transduces the signal from the cytoplasm to the nucleus where Smad regulates the transcription of the target genes through the direct association with the specific biding elements or with assistance of other transcription factors or co-activators such as p300/CBP.