Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPARγ expression and enhancing Runx2 expression.

Adipogenesis and osteogenesis, a reciprocal relationship in bone marrow, are complex processes including proliferation of precursor cells, commitment to the specific lineage, and terminal differentiation. Accumulating evidence from in vitro and in vivo studies suggests that melatonin affects terminal differentiation of osteoblasts and adipocytes, but little is known about the effect of melatonin on the process of adipogenesis and osteogenesis, especially adipogenesis. This study was performed to determine the effect of melatonin on adipogenesis and osteogenesis in human mesenchymal stem cells (hMSCs). Cell proliferation assays demonstrated that melatonin had no apparent effect on the proliferation of hMSCs. When melatonin was added to the adipogenic/osteogenic medium, it directly inhibited adipogenesis and simultaneously promoted osteogenesis of hMSCs in a dose-dependent manner. Furthermore, quantitative RT-PCR demonstrated that melatonin significantly suppressed peroxisome proliferator-activated receptor gamma (PPARγ) expression (day 3, 25% decrease; day 6, 47% decrease), but promoted Runx2 expression (day 3, 87% increase; day 6, 56% increase) in the early stages of adipogenesis and osteogenesis of hMSCs. Moreover, melatonin down-regulated several markers of terminal adipocyte differentiation, including leptin (30%), lipoprotein lipase (LPL, 41%), adiponectin (51%), and adipocyte protein 2 (αP2, 45%). Meanwhile, melatonin up-regulated several markers of osteoblast differentiation, including alkaline phosphatase (110%), osteopontin (218%), and osteocalcin (310%). These results suggest that melatonin directly inhibits hMSCs adipogenic differentiation and significantly enhances hMSCs osteogenic differentiation by suppressing PPARγ expression and enhancing Runx2 expression; this provides further evidence for melatonin as an anti-osteoporosis drug.

Zhang L ，Su P ，Xu C ，Chen C ，Liang A ，Du K ，Peng Y ，Huang D ... -  《-》

Osteogenic differentiation of human mesenchymal stem cells cultured with dexamethasone, vitamin D3, basic fibroblast growth factor, and bone morphogenetic protein-2.

Mostafa NZ ，Fitzsimmons R ，Major PW ，Adesida A ，Jomha N ，Jiang H ，Uludağ H ... -  《-》

PPARγ suppression inhibits adipogenesis but does not promote osteogenesis of human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are the common progenitors of osteoblasts and adipocytes. A reciprocal relationship exists between osteogenesis and adipogenesis in the bone marrow, and the identification of signaling pathways that stimulate MSC osteogenesis at the expense of adipogenesis is of great importance from the viewpoint of developing new therapeutic treatments for bone loss. The adipogenic transcription factor peroxisome proliferator-activated receptor γ (PPARγ) has been reported to play a vital role in modulating mesenchymal lineage allocation within the bone marrow compartment, stimulating adipocyte development at the expense of osteoblast differentiation. Hence, PPARγ may be a valuable target for drugs intended to enhance bone mass. However, little direct evidence is available for the role played by PPARγ in human mesenchymal lineage allocation. In this study, using human MSCs as an in vitro model, we showed that the two isoforms of PPARγ, PPARγ1 and PPARγ2, were differentially induced during hMSC adipogenesis, whereas only PPARγ1 was detected during osteogenesis. BADGE and GW9662, two potential antagonists of PPARγ, as well as lentivirus-mediated knockdown of PPARγ, inhibited hMSC adipogenesis but did not significantly affect osteogenesis. PPARγ knockdown did not significantly influence the expression level of the osteogenic transcription factor Runx2. Together, these results suggest that PPARγ is not the master factor regulating mesenchymal lineage determination in human bone marrow.

Yu WH ，Li FG ，Chen XY ，Li JT ，Wu YH ，Huang LH ，Wang Z ，Li P ，Wang T ，Lahn BT ，Xiang AP ... -  《-》

Could the effect of modeled microgravity on osteogenic differentiation of human mesenchymal stem cells be reversed by regulation of signaling pathways?

Zheng Q ，Huang G ，Yang J ，Xu Y ，Guo C ，Xi Y ，Pan Z ，Wang J ... -  《BIOLOGICAL CHEMISTRY》

Osteogenic growth peptide C-terminal pentapeptide [OGP(10-14)] acts on rat bone marrow mesenchymal stem cells to promote differentiation to osteoblasts and to inhibit differentiation to adipocytes.

Chen ZX ，Chang M ，Peng YL ，Zhao L ，Zhan YR ，Wang LJ ，Wang R ... -  《regulatory peptides》