| RRC ID |
19625
|
| 著者 |
Takarada T, Hojo H, Iemata M, Sahara K, Kodama A, Nakamura N, Hinoi E, Yoneda Y.
|
| タイトル |
Interference by adrenaline with chondrogenic differentiation through suppression of gene transactivation mediated by Sox9 family members.
|
| ジャーナル |
Bone
|
| Abstract |
In contrast to osteoblasts, little attention has been paid to the functional expression of adrenergic signaling machineries in chondrocytes. Expression of mRNA was for the first time demonstrated for different adrenergic receptor (AdR) subtypes in chondrogenic ATDC5 cells and mouse metatarsals isolated before vascularization in culture, but not for other molecules related to adrenergic signaling. In neonatal mouse tibial sections, beta(2)AdR and alpha(2a)AdR mRNA expression was found in chondrocytes at different developmental stages by in situ hybridization. Exposure to adrenaline significantly suppressed expression of several maturation markers through the cAMP/protein kinase A pathway activated by beta(2)AdR without affecting cellular proliferation in both cultured ATDC5 cells and metatarsals. Adrenaline also significantly inhibited gene transactivation by sry-type HMG box 9 (Sox9) family members essential for chondrogenic differentiation in a manner prevented by the general betaAdR antagonist propranolol, with a concomitant significant decrease in the levels of Sox6 mRNA and corresponding protein, in ATDC5 cells and primary cultured mouse costal chondrocytes. Systemic administration of propranolol significantly promoted the increased expression of mRNA for collagen I and collagen X, but not for collagen II, in callus of fractured femur in mice. These results suggest that adrenaline may interfere with chondrogenic differentiation through downregulation of Sox6 expression for subsequent suppression of gene transactivation mediated by Sox9 family members after activation of beta(2)AdR expressed by chondrocytes.
|
| 巻・号 |
45(3)
|
| ページ |
568-78
|
| 公開日 |
2009-9-1
|
| DOI |
10.1016/j.bone.2009.05.004
|
| PII |
S8756-3282(09)01582-8
|
| PMID |
19446054
|
| MeSH |
Adrenergic beta-2 Receptor Antagonists
Animals
Animals, Newborn
Cell Differentiation
Cells, Cultured
Chondrocytes / cytology*
Chondrocytes / metabolism
Cyclic AMP / metabolism
Embryo, Mammalian
Epinephrine / pharmacology*
Fractures, Bone / metabolism
Fractures, Bone / pathology
Metatarsal Bones / cytology
Metatarsal Bones / physiology
Mice
RNA, Messenger / biosynthesis
Receptors, Adrenergic, alpha-2 / biosynthesis*
Receptors, Adrenergic, alpha-2 / genetics
Receptors, Adrenergic, beta-2 / biosynthesis*
Receptors, Adrenergic, beta-2 / genetics
SOX9 Transcription Factor / physiology*
SOXD Transcription Factors / metabolism
Signal Transduction
Tibia / metabolism
Transcriptional Activation*
|
| IF |
4.147
|
| 引用数 |
14
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
