title: Cultured human periosteal-derived cells have inducible adipogenic activity and can also differentiate into osteoblasts in a perioxisome proliferator-activated receptor-mediated fashion.
abstract: We investigated the adipogenic activity of cultured human periosteal-derived cells and studied perioxisome proliferator-activated receptor (PPAR) ligand-mediated differentiation of cultured human periosteal-derived cells into osteoblasts. Periosteal-derived cells expressed adipogenic markers, including CCAAT/enhancer binding protein α (C/EBP- α), C/EBP-δ, aP2, leptin, LPL, and PPARγ. Lipid vesicles were formed in the cytoplasm of periosteal-derived cells. Thus, periosteal-derived cells have potential adipogenic activity. The PPARα and PPARγ agonists, WY14643 and pioglitazone, respectively, did not modulate alkaline phosphatase (ALP) activity in periosteal-derived cells during induced osteoblastic differentiation, however, the PPARα and PPARγ antagonists, GW6471 and T0070907, respectively, both decreased ALP activity in these cells. WY14643 did not affect, whereas pioglitazone enhanced, alizarin red-positive mineralization and calcium content in the periosteal-derived cells. GW6471 and T0070907 both decreased mineralization and calcium content. By RT-PCR, pioglitazone significantly increased ALP expression in periosteal-derived cells between culture day 3 and 2 weeks. Pioglitazone increased Runx2 expression after 3 days, which declined thereafter, but did not alter osteocalcin expression. Both of GW6471 and T0070907 decreased ALP mRNA expression. These results suggest that pioglitazone enhances osteoblastic differentiation of periosteal-derived cells by increasing Runx2 and ALP mRNA expression, and increasing mineralization. GW6471 and T0070907 inhibit osteoblastic differentiation of the periosteal-derived cells by decreasing ALP expression and mineralization in the periosteal-derived cells. In conclusion, although further study will be needed to clarify the mechanisms of PPAR-regulated osteogenesis, our results suggest that PPARγ agonist stimulates osteoblastic differentiation of cultured human periosteal-derived cells and PPARα and PPARγ antagonists inhibit osteoblastic differentiation in these cells.
authors.affiliation: 1. Clinical Research Institute of Gyeongsang National University Hospital, Jinju, Republic of Korea;
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.affiliation: 2. Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;
authors.forename: Hyun-Ho
authors.initials: HH
authors.lastname: Joo
authors.affiliation: 2. Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kang
authors.affiliation: 2. Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;
authors.forename: Bong-Wook
authors.initials: BW
authors.lastname: Park
authors.affiliation: 3. 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: 4. Department of Thoracic and Cardiovascular Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: 5. Department of Oral and Maxillofacial Surgery, College of Medicine, Ulsan University, Ulsan, Republic of Korea;
authors.forename: Iel-Yong
authors.initials: IY
authors.lastname: Sung
authors.affiliation: 6. OBS/Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea;
authors.forename: Gyu-Jin
authors.initials: GJ
authors.lastname: Rho
authors.affiliation: 7. 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: 2. Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;
authors.forename: June-Ho
authors.initials: JH
authors.lastname: Byun
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D010080:Oxazoles / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors; D010521:Periosteum / Q000166:cytology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077205:Pioglitazone; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001549:Benzamides; C449302:GW 6471; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D011725:Pyridines; D011743:Pyrimidines; C458508:T 0070907; D045162:Thiazolidinediones; D014443:Tyrosine; C006253:pirinixic acid; D000077205:Pioglitazone
keywords: Adipogenic activity; Osteoblastic differentiation; PPAR ligands.; Periosteal-derived cells