Source:http://linkedlifedata.com/resource/pubmed/id/11315999
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2001-4-23
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| pubmed:abstractText |
Subchondral bone sclerosis may be important for the onset and/or progression of cartilage loss/damage in human osteoarthritis (OA). OA osteoblasts are resistant to parathyroid hormone (PTH) stimulation, which could explain bone sclerosis via the inhibition of PTH-dependent catabolism. Here, we investigated the molecular mechanism(s) responsible for reduced PTH-dependent cyclic adenosine monophosphate (cAMP) synthesis in OA subchondral osteoblasts. Although cholera toxin (CTX) increased basal cAMP formation in these cells, it failed to stimulate PTH-dependent cAMP synthesis, whereas pertussis toxin (PTX) did not inhibit basal cAMP, yet diminished PTH-dependent cAMP production. Binding of 125I-PTH indicated lower PTH receptor levels in OA than in normal osteoblasts (-50.5 +/- 9.5%). This could be attributed to either reduced expression of the PTH receptor (PTH-R) or altered recycling of existing pools of receptors. Reverse-transcription polymerase chain reaction (RT-PCR) analysis indicated decreased PTH-R messenger RNA (mRNA) levels in OA cells that were highly variable (ranging from -10% to -60%), a situation that reflects disease severity. Interestingly, OA osteoblasts produced more prostaglandin E2 (PGE2) than normal osteoblasts, and using naproxen, a cyclo-oxygenase inhibitor, increased PTH-dependent cAMP formation to a level similar to normal osteoblasts. Because heterologous desensitization can explain a decrease in PTH binding but cannot account for reduced PTH-R expression, we looked at the possible effect of insulin-like growth factor 1 (IGF-1) on this parameter. Blocking IGF-1 signaling with a neutralizing receptor antibody increased 125I-PTH binding in both normal and OA osteoblasts. Conversely, treatments with IGF-1 receptor (IGF-1R) antibody only slightly increased the levels of PTH-R mRNA whereas the addition of IGF-1 significantly reduced PTH-R mRNA levels (-24.1 +/- 7.1%), yet neither PGE2 nor naproxen modified PTH-R levels. These results suggest that both IGF-1 signaling and PGE2 formation repress PTH-dependent response in OA osteoblasts, a situation that can contribute to abnormal bone remodeling and bone sclerosis in OA.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Naproxen,
http://linkedlifedata.com/resource/pubmed/chemical/Parathyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Parathyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0884-0431
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
16
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
713-21
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11315999-Aged,
pubmed-meshheading:11315999-Aged, 80 and over,
pubmed-meshheading:11315999-Bone Remodeling,
pubmed-meshheading:11315999-Cells, Cultured,
pubmed-meshheading:11315999-Cholera Toxin,
pubmed-meshheading:11315999-Cyclic AMP,
pubmed-meshheading:11315999-Cyclooxygenase Inhibitors,
pubmed-meshheading:11315999-Dinoprostone,
pubmed-meshheading:11315999-Female,
pubmed-meshheading:11315999-Gene Expression Regulation,
pubmed-meshheading:11315999-Humans,
pubmed-meshheading:11315999-Insulin-Like Growth Factor I,
pubmed-meshheading:11315999-Male,
pubmed-meshheading:11315999-Middle Aged,
pubmed-meshheading:11315999-Naproxen,
pubmed-meshheading:11315999-Osteoarthritis,
pubmed-meshheading:11315999-Osteoblasts,
pubmed-meshheading:11315999-Parathyroid Hormone,
pubmed-meshheading:11315999-Pertussis Toxin,
pubmed-meshheading:11315999-RNA, Messenger,
pubmed-meshheading:11315999-Receptor, IGF Type 1,
pubmed-meshheading:11315999-Receptors, Parathyroid Hormone,
pubmed-meshheading:11315999-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11315999-Second Messenger Systems,
pubmed-meshheading:11315999-Virulence Factors, Bordetella
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| pubmed:year |
2001
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| pubmed:articleTitle |
Endogenous prostaglandin E2 and insulin-like growth factor 1 can modulate the levels of parathyroid hormone receptor in human osteoarthritic osteoblasts.
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| pubmed:affiliation |
Osteoarthritis Research Unit, H pital Notre-Dame, Centre Hospitalier de l'Université de Montréal, Québec, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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