title: FOXO1 Is Involved in the Effects of Cigarette Smoke Extract on Osteoblastic Differentiation of Cultured Human Periosteum-derived Cells.
abstract: Cigarette smoke is associated with delayed fracture healing, alterations in mineral content, and osteoporosis, however, its effects on osteoblastic differentiation of osteoprogenitor cells are not fully understood. In the present study, we examined the effects of cigarette smoke extract (CSE) on osteoblastic differentiation of cultured human periosteum-derived cells. We found that CSE inhibited alkaline phosphatase (ALP) activity, mineralization and Runx2 transactivation of the periosteum-derived cells. Nucleofection of RUNX2 into the periosteum-derived cells increased expression of endogenous osteocalcin (OC) and ALP genes in osteogenic induction medium and increased OC expression in non-osteogenic medium. Treatment of the periosteum-derived cells with CSE resulted in decreased phosphorylation of AKT and forkhead box protein O1 (FOXO1). The AKT phosphorylation-resistant mutant, FOXO1-A3, inhibited transcriptional activity of RUNX2 in the periosteum-derived cells. The current study suggests one mechanism by which CSE exposure leads to inhibition of osteoblastic differentiation of cultured human periosteum-derived cells.
authors.affiliation: 1. 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: 1. Department of Oral and Maxillofacial Surgery, College of Medicine, Ulsan University, Ulsan, Republic of Korea.
authors.forename: Bong-Chan
authors.initials: BC
authors.lastname: Park
authors.affiliation: 2. 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. Clinical Research Institute of Gyeongsang National University Hospital, Jinju, Republic of Korea.
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Cho
authors.affiliation: 2. Clinical Research Institute of Gyeongsang National University Hospital, Jinju, Republic of Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: 3. 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, Republic of Korea.
authors.forename: Bong-Wook
authors.initials: BW
authors.lastname: Park
authors.affiliation: 3. 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, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kang
authors.affiliation: 4. Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
authors.forename: Ho-Cheol
authors.initials: HC
authors.lastname: Kim
authors.affiliation: 5. 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: 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. Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors.forename: Uk-Kyu
authors.initials: UK
authors.lastname: Kim
authors.affiliation: 8. 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: 9. Department of Nanobiomedical Science, Dankook university, Cheonan, Republic of Korea.
authors.forename: Se-Heang
authors.initials: SH
authors.lastname: Oh
authors.affiliation: 3. 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, Republic of Korea.
authors.forename: June-Ho
authors.initials: JH
authors.lastname: Byun
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000235:genetics; D010521:Periosteum / Q000166:cytology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D012906:Smoke; D015675:Osteocalcin; D000469:Alkaline Phosphatase
keywords: FOXO1; Osteoblastic differentiation; Periosteum-derived cells; RUNX2 activity