Bone and calcium update; bone research update. Regulatory mechanisms in osteoblast differentiation
Department Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Japan. Clinical calcium
Differentiation process of osteoblasts, which play a central role in bone formation, is harmoniously controlled by several cytokines and hormones. Particularly, Bone Morphogenetic Protein (BMP) , Indian Hedgehog (Ihh) , and Wnt family proteins are important cytokines for osteoblast differentiation. Understandings of molecular mechanisms by which these cytokines stimulate osteoblast differentiation have been extensively investigated. BMP/Smad signaling, canonical Wnt pathway, non-canonical Wnt pathway and Ihh/Gli signaling play critical role in osteoblast differentiation. Furthermore, biochemical and genetic studies have demonstrated important roles of Runt related transcription factor 2 (Runx2) , Osterix, Activating transcription factor 4 (ATF4) , Msh homeobox 2 (Msx2) and Oasis for osteoblast differentiation. Thus, these milestone studies have dramatically progressed in our understanding of the cellular and molecular mechanisms of osteoblast differentiation for 20 years.
Available from: Youlang Zhou
- "Under the action of related growth factors, MSCs gradually differentiate into osteogenic cells and synthesize extracellular matrix, including collagen, and ultimately transform into mature bone tissue (2). Number and function abnormalities of cytokines and growth factors directly cause weak differentiation of MSCs to osteoblasts, leading to osteoporosis and fracture healing disorders (3). A large amount of growth factors, including bone morphogenetic protein (BMP), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) in the extracellular matrix and on cell membrane surfaces are ingested and controlled by the heparan sulfate (HS) lateral chains of heparan sulfate proteoglycans (HSPGs) (4). "
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ABSTRACT: Heparanase (HPSE) is a type of endoglycosidase that decomposes the heparan sulfate (HS) lateral chains of heparan sulfate proteoglycans (HSPGs), releases related growth factors and participates in angiogenesis and bone formation. HPSE is expressed in osteoblasts and is involved in fracture healing. However, the role of HPSE in osteogenic differentiation requires in-depth investigation. To investigate the expression of HPSE in the osteogenic differentiation of rat marrow stromal cells (MSCs), the protein and mRNA expression levels of HPSE on days 0, 1, 3, 7, 10, 14 and 21 of osteogenic differentiation of MSCs in 2- and 10-month-old rats were detected using western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively. From the third day of osteogenic differentiation onwards, all HPSE protein and mRNA expression levels in 2-month-old rats were significantly increased compared with basal levels (days 0 and 1; P<0.05). The protein and mRNA expression levels reached a peak on days 10 and 14, respectively, followed by a gradual decline. The same pattern was observed in 10-month-old rats; however, when compared with with basal levels, the differences were not statistically significant (P>0.05). The protein and mRNA levels of HPSE in the 2-month-old rats were significantly higher compared with the respective levels in the 10-month-old rats (P<0.05). HPSE is involved in the osteogenic differentiation of rat MSCs. The protein and mRNA expression levels of HPSE in aged rats are weaker compared with those in young rats, which may be related to the declined osteogenic differentiation ability.
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