Xiao Zhang1,2, Jing Guo3, Gang Wu2, Yongsheng Zhou1,4. 1. Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China. 2. Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, 1081 LA, Amsterdam, the Netherland. 3. Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, 1081 LA, Amsterdam, the Netherland. 4. National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Abstract
OBJECTIVE: Roles of bone morphogenetic proteins (BMPs) on osteogenesis of human adipose-derived stem cells (hASCs) remain ambiguous. In this study, we evaluated in vitro and in vivo functional characteristics of BMPs of different dimerization types, with the aim of determining osteoinductive efficiency of heterodimeric BMP-2/7 on osteogenesis of hASCs. MATERIALS AND METHODS: We explored osteoinductive effects of three different BMPs by using cell DNA assay, alkaline phosphatase (ALP) activity assay, alizarin red staining and mineralization assay, and real-time PCR, in vitro. Also, we examined ectopic bone formation in nude mice by using soft X-ray, histomorphometric and immunohistochemical analyses in vivo. RESULTS: In our dose-response study, we showed that BMPs with both dimerization types did not induce in vitro osteogenesis of hASCs without osteogenic medium (OM). In the presence of OM, BMPs significantly enhanced hASC osteogenesis in a dose-dependent manner. In in vivo experiments, our analyses indicated that BMPs promoted osteogenesis of hASCs without in vitro osteogenic induction. However, both in vitro and in vivo, there were no significant differences in hASC osteogenic induction between heterodimeric and homodimeric BMPs. CONCLUSIONS: Heterodimeric BMP-2/7 significantly promoted osteogenesis of hASCs in vitro and in vivo. However, BMP-2/7 was not found to be a stronger inducer of osteogenesis compared to homodimeric either BMP-2 or BMP-7.
OBJECTIVE: Roles of bone morphogenetic proteins (BMPs) on osteogenesis of human adipose-derived stem cells (hASCs) remain ambiguous. In this study, we evaluated in vitro and in vivo functional characteristics of BMPs of different dimerization types, with the aim of determining osteoinductive efficiency of heterodimeric BMP-2/7 on osteogenesis of hASCs. MATERIALS AND METHODS: We explored osteoinductive effects of three different BMPs by using cell DNA assay, alkaline phosphatase (ALP) activity assay, alizarin red staining and mineralization assay, and real-time PCR, in vitro. Also, we examined ectopic bone formation in nude mice by using soft X-ray, histomorphometric and immunohistochemical analyses in vivo. RESULTS: In our dose-response study, we showed that BMPs with both dimerization types did not induce in vitro osteogenesis of hASCs without osteogenic medium (OM). In the presence of OM, BMPs significantly enhanced hASC osteogenesis in a dose-dependent manner. In in vivo experiments, our analyses indicated that BMPs promoted osteogenesis of hASCs without in vitro osteogenic induction. However, both in vitro and in vivo, there were no significant differences in hASC osteogenic induction between heterodimeric and homodimeric BMPs. CONCLUSIONS: Heterodimeric BMP-2/7 significantly promoted osteogenesis of hASCs in vitro and in vivo. However, BMP-2/7 was not found to be a stronger inducer of osteogenesis compared to homodimeric either BMP-2 or BMP-7.
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