Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2009-5-11
pubmed:abstractText
It has been reported that anti-inflammatory drugs (AIDs) inhibited bone repair in animal studies, and suppressed proliferation and induced cell death in rat osteoblast cultures. In this study, we further investigated the molecular mechanisms of AID effects on proliferation and cell death in human osteoblasts (hOBs). We examined the effects of dexamethasone (10(-7) and 10(-6)M), non-selective non-steroidal anti-inflammatory drugs (NSAIDs): indomethacin, ketorolac, piroxicam and diclofenac (10(-5) and 10(-4)M), and COX-2 inhibitor: celecoxib (10(-6) and 10(-5)M) on proliferation, cytotoxicity, cell death, and mRNA and protein levels of cell cycle and apoptosis-related regulators in hOBs. All the tested AIDs significantly inhibited proliferation and arrested cell cycle at G0/G1 phase in hOBs. Celecoxib and dexamethasone, but not non-selective NSAIDs, were found to have cytotoxic effects on hOB, and further demonstrated to induce apoptosis and necrosis (at higher concentration) in hOBs. We further found that indomethacin, celecoxib and dexamethasone increased the mRNA and protein expressions of p27(kip1) and decreased those of cyclin D2 and p-cdk2 in hOBs. Bak expression was increased by celecoxib and dexamethasone, while Bcl-XL level was declined only by dexamethasone. Furthermore, the replenishment of PGE1, PGE2 or PGF2alpha did not reverse the effects of AIDs on proliferation and expressions of p27(kip1) and cyclin D2 in hOBs. We conclude that the changes in expressions of regulators of cell cycle (p27(kip1) and cyclin D2) and/or apoptosis (Bak and Bcl-XL) by AIDs may contribute to AIDs caused proliferation suppression and apoptosis in hOBs. This effect might not relate to the blockage of prostaglandin synthesis by AIDs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A5, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2 Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone, http://linkedlifedata.com/resource/pubmed/chemical/Diclofenac, http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin, http://linkedlifedata.com/resource/pubmed/chemical/Ketorolac, http://linkedlifedata.com/resource/pubmed/chemical/L-Lactate Dehydrogenase, http://linkedlifedata.com/resource/pubmed/chemical/Piroxicam, http://linkedlifedata.com/resource/pubmed/chemical/Propidium, http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/Thymidine, http://linkedlifedata.com/resource/pubmed/chemical/celecoxib
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
258
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
148-56
pubmed:meshHeading
pubmed-meshheading:19428934-Annexin A5, pubmed-meshheading:19428934-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:19428934-Apoptosis, pubmed-meshheading:19428934-Cell Cycle, pubmed-meshheading:19428934-Cell Proliferation, pubmed-meshheading:19428934-Cells, Cultured, pubmed-meshheading:19428934-Cyclooxygenase 2 Inhibitors, pubmed-meshheading:19428934-Dexamethasone, pubmed-meshheading:19428934-Diclofenac, pubmed-meshheading:19428934-Dose-Response Relationship, Drug, pubmed-meshheading:19428934-Humans, pubmed-meshheading:19428934-Immunohistochemistry, pubmed-meshheading:19428934-Indomethacin, pubmed-meshheading:19428934-Ketorolac, pubmed-meshheading:19428934-L-Lactate Dehydrogenase, pubmed-meshheading:19428934-Osteoblasts, pubmed-meshheading:19428934-Piroxicam, pubmed-meshheading:19428934-Propidium, pubmed-meshheading:19428934-Pyrazoles, pubmed-meshheading:19428934-RNA, Messenger, pubmed-meshheading:19428934-Sulfonamides, pubmed-meshheading:19428934-Thymidine
pubmed:year
2009
pubmed:articleTitle
Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts.
pubmed:affiliation
Department of Orthopaedics, Kaohsiung Medical University, Kaohsiung, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't