title: Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice.
abstract: PPARγ has critical role in the differentiation of mesenchymal stem cells into adipocytes while suppressing osteoblastic differentiation. We generated transgenic mice that overexpress PPARγ specifically in osteoblasts under the control of a 2.3-kb procollagen type 1 promoter (Col.1-PPARγ). Bone mineral density (BMD) of 6- to 14-week-old Col.1 - PPARγ male mice was 8% to 10% lower than that of their wild-type littermates, whereas no difference was noticed in Col.1-PPARγ female mice. Col.1-PPARγ male mice exhibited decreased bone volume (45%), trabecular thickness (23%), and trabecular number (27%), with a reciprocal increase in trabecular spacing (51%). Dynamic histomorphometric analysis also revealed that bone-formation rate (42%) and mineral apposition rate (32%) were suppressed significantly in Col.1-PPARγ male mice compared with their wild-type littermates. Interestingly, osteoclast number and surface also were decreased by 40% and 58%, respectively, in Col.1-PPARγ male mice. In vitro whole-marrow culture for osteoclastogenesis also showed a significant decrease in osteoclast formation (approximately 35%) with the cells from Col.1-PPARγ male mice, and OPG/RANKL ratio was reduced in stromal cells from Col.1-PPARγ male mice. Although there was no significant difference in BMD in Col.1-PPARγ female mice up to 30 weeks, bone loss was accelerated after ovariectomy compared with wild-type female mice (-3.9% versus -6.8% at 12 weeks after ovariectomy, p < .01), indicating that the effects of PPARγ overexpression becomes more evident in an estrogen-deprived state in female mice. In conclusion, in vivo osteoblast-specific overexpression of PPARγ negatively regulates bone mass in male mice and accelerates estrogen-deficiency-related bone loss in female mice.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Cho
authors.forename: Jae-Yeon
authors.initials: JY
authors.lastname: Yang
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Her
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Jung
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Sun
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: An
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Cho
authors.forename: Sang Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Seong Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Wook-Young
authors.initials: WY
authors.lastname: Baek
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Mijung
authors.initials: M
authors.lastname: Yim
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D015519:Bone Density; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002457:Cell Extracts; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis; D010052:Ovariectomy; D047495:PPAR gamma / Q000378:metabolism*; D010641:Phenotype; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D002457:Cell Extracts; D047495:PPAR gamma