title: Changes in the mRNA expression of osteoblast-related genes in response to beta(3)-adrenergic agonist in UMR106 cells.
abstract: Activation of adrenergic receptors (AR) was demonstrated to result in either bone gain or bone loss depending on the activated AR subtypes and concentrations of agonists used. While beta(2)-AR agonist was extensively investigated as an osteopenic agent, effects of beta(3)-AR activation on osteoblasts were still elusive. Rat osteoblast-like UMR106 cells were herein found to express several AR subtypes, including beta(3)-AR. After exposure to a low-dose beta(3)-AR agonist BRL37344 (10 nmol L(-1)), UMR106 cells downregulated the mRNA expression of transcription factors Runx2 and Dlx5, which are important for initiation of osteoblast differentiation. Low-dose BRL37344 also decreased the expression ratio of receptor activator of nuclear factor kappaB ligand (RANKL) over osteoprotegerin (OPG), suggesting the protective effect of beta(3)-AR agonist against bone resorption. Alkaline phosphatase expression was markedly decreased, whereas expressions of osteocalcin and osteopontin were increased by 100 nmol L(-1) BRL37344, indicating that beta(3)-AR activation could accelerate the transition of matrix maturation stage to mineralization stage. In conclusion, beta(3)-AR activation in rat osteoblasts induced alteration in the expression of osteoblast-related transcription factor genes as well as genes required for bone formation and resorption. The present results also suggest that, besides beta(2)-AR, beta(3)-AR is another AR subtype responsible for the sympathetic nervous system-induced bone remodeling.
authors.affiliation: Department of Physiology, Mahidol University, Bangkok, Thailand.
authors.forename: Amporn
authors.initials: A
authors.lastname: Nuntapornsak
authors.forename: Kannikar
authors.initials: K
authors.lastname: Wongdee
authors.forename: Jirawan
authors.initials: J
authors.lastname: Thongbunchoo
authors.forename: Nateetip
authors.initials: N
authors.lastname: Krishnamra
authors.forename: Narattaphol
authors.initials: N
authors.lastname: Charoenphandhu
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D058667:Adrenergic beta-3 Receptor Agonists; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000322:Adrenergic Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D050659:Core Binding Factor Alpha 1 Subunit; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D014157:Transcription Factors; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase