Mesenchymal stromal cells (MSCs) are multipotent cells that can give rise to different cell types of the mesodermal lineages. They are powerful sources for cell therapy in regenerative medicine as they can be isolated from various tissues, and can be expanded and induced to differentiate into multiple lineages. Recently, the umbilical cord has been suggested as an alternative source of MSCs. Although MSCs derived from the umbilical cord can be induced to differentiate into osteoblasts with a phenotypic similarity to that of bone marrow-derived MSCs, the differentiation ability is not consistent. In addition, MSCs from the umbilical cord require a longer period of time to differentiate into osteoblasts. Previous studies have demonstrated the benefits of bone morphogenetic protein-2 (BMP-2) in bone tissue regeneration. In addition, several studies have supported the use of BMP-2 in periodontal regeneration, sinus lift bone-grafting and non-unions in oral surgery. Although the use of BMP-2 for bone tissue regeneration has been extensively investigated, the BMP-2-induced osteogenic differentiation of MSCs derived from the umbilical cord has not yet been fully examined. Therefore, in this study, we aimed to examine the effects of BMP-2 on the osteogenic differentiation of MSCs derived from umbilical cord compared to that of MSCs derived from bone marrow. The degree of osteogenic differentiation following BMP-2 treatment was determined by assessing alkaline phosphatase (ALP) activity, and the expression profiles of osteogenic differentiation marker genes, osterix (Osx), Runt-related transcription factor 2 (Runx2) and osteocalcin (Ocn). The results revealed that BMP-2 enhanced the osteogenic differentiation capacity of MSCs derived from both bone marrow and umbilical cord as demonstrated by increased ALP activity and the upregulation of osteogenic differentiation marker genes. The enhancement of the osteogenic differentiation capacity of MSCs by BMP-2 suggests that these MSCs may be used as alternative sources for bone engineering or cell therapy in regenerative medicine.

Background: Diarylheptanoid (ASPP 049) isolated from C. comosa exhibits high estrogenic activity. Results: ASPP 049 rapidly induced ␤-catenin accumulation in the nucleus and activated TCF/LEF-mediated activation of Wnt/␤-catenin signaling. Conclusion: ASPP 049 from C. comosa induces preosteoblastic cell proliferation and differentiation through activation of Wnt/␤-catenin signaling. Significance: Providing a scientific rationale for using C. comosa as a dietary supplement to prevent bone loss in postmenopausal women.

Most type 2 diabetic patients are obese who have increased number of visceral adipocytes. Those visceral adipocytes release several factors that enhance insulin resistance making diabetic treatment ineffective. It is known that significant percentages of visceral adipocytes are derived from mesenchymal stem cells and high glucose enhances adipogenic differentiation of mouse bone marrow-derived MSCs (BM-MSCs). However, the effect of high glucose on adipogenic differentiation of human bone marrow and gestational tissue-derived MSCs is still poorly characterized. This study aims to investigate the effects of high glucose on proliferation as well as adipogenic and osteogenic differentiation of human MSCs derived from bone marrow and several gestational tissues including chorion, placenta, and umbilical cord. We found that high glucose reduced proliferation but enhanced adipogenic differentiation of all MSCs examined. The expression levels of some adipogenic genes were also upregulated when MSCs were cultured in high glucose. Although high glucose transiently downregulated the expression levels of some osteogenic genes examined, its effect on the osteogenic differentiation levels of the MSCs is not clearly demonstrated. The knowledge gained from this study will increase our understanding about the effect of high glucose on adipogenic differentiation of MSCs and might lead to an improvement in the diabetic treatment in the future.

Curcuma comosa Roxb. is ginger-family plant used to relieve menopausal symptoms. Previous work showed that C. comosa extracts protect mice from ovariectomy-induced osteopenia with minimal effects on reproductive organs, and identified the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD) as the major active component of C. comosa rhizomes. At 1–10 μM, DPHD increased differentiation in transformed mouse osteoblasts, but the effect of DPHD on normal bone cells was unknown. We examined the concentration dependency and mechanism of action of DPHD relative to 17β-estradiol in nontransformed human osteoblasts (h-OB). The h-OB were 10–100 fold more sensitive to DPHD than transformed osteoblasts: DPHD increased h-OB proliferation at 10 nM and, at 100 nM, activated MAP kinase signaling within 30 minutes. In long-term differentiation assays, responses of h-OB to DPHD were significant at 10 nM, and optimal response in most cases was at 100 nM. At 7–21 days, DPHD accelerated osteoblast differentiation, indicated by alkaline phosphatase activity and osteoblast-specific mRNA production. Effects of DPHD were eliminated by the estrogen receptor antagonist ICI182780. During differentiation, DPHD promoted early expression of osteoblast transcription factors, RUNX2 and osterix. Subsequently, DPHD accelerated production of bone structural genes, including COL1A1 and osteocalcin comparably to 17β-estradiol. In h-OB, DPHD increased the osteoprotegerin to RANKL ratio and supported mineralization more efficiently than 10 nM 17β-estradiol. We conclude that DPHD promotes human osteoblast function in vitro effectively at nanomolar concentrations, making it a promising compound to protect bone in menopausal women.