title: Cultured Human Periosteum-Derived Cells Can Differentiate into Osteoblasts in a Perioxisome Proliferator-Activated Receptor Gamma-Mediated Fashion via Bone Morphogenetic Protein signaling.
abstract: The differentiation of mesenchymal stem cells towards an osteoblastic fate depends on numerous signaling pathways, including activation of bone morphogenetic protein (BMP) signaling components. Commitment to osteogenesis is associated with activation of osteoblast-related signal transduction, whereas inactivation of this signal transduction favors adipogenesis. BMP signaling also has a critical role in the processes by which mesenchymal stem cells undergo commitment to the adipocyte lineage. In our previous study, we demonstrated that an agonist of the perioxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipocyte differentiation, stimulates osteoblastic differentiation of cultured human periosteum-derived cells. In this study, we used dorsomorphin, a selective small molecule inhibitor of BMP signaling, to investigate whether BMP signaling is involved in the positive effects of PPARγ agonists on osteogenic phenotypes of cultured human periosteum-derived cells. Both histochemical detection and bioactivity of ALP were clearly increased in the periosteum-derived cells treated with the PPARγ agonist at day 10 of culture. Treatment with the PPARγ agonist also caused an increase in alizarin red S staining and calcium content in the periosteum-derived osteoblasts at 2 and 3 weeks of culture. In contrast, dorsomorphin markedly decreased ALP activity, alizarin red S staining and calcium content in both the cells treated with PPARγ agonist and the cells cultured in osteogenic induction media without PPARγ agonist during the culture period. In addition, the PPARγ agonist clearly increased osteogenic differentiation medium-induced BMP-2 upregulation in the periosteum-derived osteoblastic cells at 2 weeks of culture as determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), immunoblotting, and immunocytochemical analyses. Although further study will be needed to clarify the mechanisms of PPARγ-regulated osteogenesis, our results suggest that the positive effects of a PPARγ agonist on the osteogenic phenotypes of cultured human periosteum-derived cells seem to be dependent on BMP signaling.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Jin-Eun
authors.initials: JE
authors.lastname: Chung
authors.affiliation: Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: Bong-Wook
authors.initials: BW
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
authors.forename: Sun-Chul
authors.initials: SC
authors.lastname: Hwang
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, Ulsan University Hospital, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Yeong-Cheol
authors.initials: YC
authors.lastname: Cho
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, Ulsan University Hospital, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Iel-Yong
authors.initials: IY
authors.lastname: Sung
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Dong Kyun
authors.initials: DK
authors.lastname: Woo
authors.affiliation: Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 660-702, Republic of Korea.
authors.forename: June-Ho
authors.initials: JH
authors.lastname: Byun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D000469:Alkaline Phosphatase / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism* / Q000502:physiology; D010012:Osteogenesis; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010521:Periosteum / Q000166:cytology*; D000077205:Pioglitazone; D061251:Primary Cell Culture; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C525718:BMP2 protein, human; D001549:Benzamides; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; C493709:RUNX2 protein, human; C458508:T 0070907; D045162:Thiazolidinediones; C516138:dorsomorphin; D055372:AMP-Activated Protein Kinases; D000469:Alkaline Phosphatase; D000077205:Pioglitazone
keywords: BMP signaling; Osteoblastic differentiation; PPARγ agonist; Periosteum-derived cells