RRC ID 61961
著者 Hutchison MR, White PC.
タイトル Prostacyclin regulates bone growth via the Epac/Rap1 pathway.
ジャーナル Endocrinology
Abstract Prostaglandins, particularly PGE2, are important to adult bone and joint health, but how prostaglandins act on growth plate cartilage to affect bone growth is unclear. We show that growth plate cartilage is distinct from articular cartilage with respect to cyclooxygenase (COX)-2 mRNA expression; although articular chondrocytes express very little COX-2, COX-2 expression is high in growth plate chondrocytes and is increased by IGF-I. In bovine primary growth plate chondrocytes, ATDC5 cells, and human metatarsal explants, inhibition of COX activity with nonsteroidal antiinflammatory drugs (NSAIDs) inhibits chondrocyte proliferation and ERK activation by IGF-I. This inhibition is reversed by prostaglandin E2 and prostacyclin (PGI2) but not by prostaglandin D2 or thromboxane B2. Inhibition of COX activity in young mice by ip injections of NSAIDs causes dwarfism. In growth plate chondrocytes, inhibition of proliferation and ERK activation by NSAIDs is reversed by forskolin, 8-bromoadenosine, 3',5'-cAMP and a prostacyclin analog, iloprost. The inhibition of proliferation and ERK activation by celecoxib is also reversed by 8CPT-2Me-cAMP, an activator of Epac, implicating the small G protein Rap1 in the pathway activated by iloprost. These results imply that prostacyclin is required for proper growth plate development and bone growth.
巻・号 156(2)
ページ 499-510
公開日 2015-2-1
DOI 10.1210/en.2014-1348
PMID 25406016
PMC PMC4298325
MeSH Animals Anti-Inflammatory Agents, Non-Steroidal Bone Development* Cattle Celecoxib Cells, Cultured Chondrocytes / enzymology Cyclooxygenase 2 / metabolism Epoprostenol / metabolism Female Growth Plate / drug effects Growth Plate / enzymology Guanine Nucleotide Exchange Factors / metabolism* Humans Iloprost Insulin-Like Growth Factor I / metabolism Male Mice Mice, Inbred C57BL Prostaglandins I / physiology* Pyrazoles Signal Transduction Sulfonamides rap1 GTP-Binding Proteins / metabolism*
IF 3.934
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)