title: Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone formation in vivo.
abstract: Molecular mechanisms underlying unloading-induced reduction of bone formation have not yet been fully understood. In vitro, Runx2 has been suggested to be involved in mechanical signaling in osteoblasts. However, the roles of Runx2 in vivo during the bone response to mechanical stimuli have not yet been known. The purpose of this paper was to examine the roles of Runx2 in unloading-induced bone loss in vivo. Tail suspension was conducted for 2 wk using 9- to 11-wk-old Runx2 heterozygous knockout mice (Runx2(+/-)) and wild-type (Wt) littermates. Bones were subjected to two-dimensional micro-x-ray computed tomography, bone histomorphometry and RT-PCR analyses. Loss of half Runx2 gene dosage-exacerbated unloading-induced bone loss in trabecular and cortical envelopes. Unloading-induced reduction in mineral apposition rate and bone formation rate in cortical bone as well as trabecular bone was exacerbated in Runx2(+/-) mice, compared with Wt mice. Bone resorption parameters were not significantly affected by unloading or Runx2(+/-) genotype. Basal Runx2 and osterix mRNA levels in bone were reduced by 50% in Wt, whereas unloading in Runx2(+/-) mice did not further alter Runx2 and osterix mRNA levels. In contrast, osteocalcin mRNA levels were reduced by unloading, regardless of Runx2 gene dosage. These data demonstrated that full Runx2 gene dosage is required for maintaining normal function of osteoblasts in mechanical unloading or nonphysiological condition. Finally, we propose Runx2 as a critical target gene in unloading to alter osteoblastic activity and bone formation in vivo.
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Japan.
authors.forename: Ruchanee
authors.initials: R
authors.lastname: Salingcarnboriboon
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tsuji
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakashima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis; D000818:Animals; D015519:Bone Density; D001846:Bone Development; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers / Q000737:chemistry; D005452:Fluoresceins / Q000737:chemistry; D018628:Gene Dosage; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015233:Models, Statistical; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013314:Stress, Mechanical; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D000596:Amino Acids; D050659:Core Binding Factor Alpha 1 Subunit; D017931:DNA Primers; D005452:Fluoresceins; D012333:RNA, Messenger; C036020:deoxypyridinoline; C007740:fluorexon