Osteogenic differentiation of mouse adipose-derived adult stromal cells requires retinoic acid and bone morphogenetic protein receptor type IB signaling.
Although the multilineage potential of human adipose-derived adult stromal cells (ADAS) has been well described, few published studies have investigated the biological and molecular mechanisms underlying osteogenic differentiation of mouse ADAS. We report here that significant osteogenesis, as determined by gene expression and histological analysis, is induced only when mouse ADAS are cultured in the presence of retinoic acid with or without recombinant human bone morphogenetic protein (BMP)-2 supplementation. Furthermore, a dynamic expression profile for the BMP receptor (BMPR) isoform IB was observed, with dramatic up-regulation during osteogenesis. Western blot analysis revealed that retinoic acid enhanced levels of BMPR-IB protein during the first 7 days of osteogenic differentiation and that RNAi-mediated suppression of BMPR-IB dramatically impaired the ability of ADAS to form bone in vitro. In contrast, absence of BMPR-IA did not significantly diminish ADAS osteogenesis. Our data therefore demonstrate that the osteogenic commitment of multipotent mouse ADAS requires retinoic acid, which enhances expression of the critical BMPR-IB isoform.
Wan
Derrick C
DC
Department of Surgery, Stanford University School of Medicine, 257 Campus Drive West, Stanford, CA 94305, USA.
Shi
Yun-Ying
YY
Nacamuli
Randall P
RP
Quarto
Natalina
N
Lyons
Karen M
KM
Longaker
Michael T
MT
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D010012:Osteogenesis / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism*
D000970:Antineoplastic Agents; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D014212:Tretinoin; D052005:Bone Morphogenetic Protein Receptors, Type I