Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular ATP acting through purinoceptors may be an important factor in the modulation of bone turnover. In this study we cloned and sequenced the P2U purinoceptor from osteoclastoma, confirming the recently published human sequence. Furthermore, by the reverse transcriptase-linked polymerase chain reaction (RT-PCR) and Southern blotting we demonstrated expression of P2U receptor mRNA in bone, primary cultures of human bone-derived cells, and two osteosarcoma cell lines, Saos2 and Te85. P2U receptor transcripts were identified in alkaline phosphatase-positive human bone-derived cells isolated by flow cytometry providing strong evidence for the expression of the P2U purinoceptor in mature osteoblasts. P2U receptor transcripts were also detected in a purified giant cell population isolated from osteoclastoma, indicating that this receptor is also expressed by osteoclasts. These data suggest that purinergic agonists may play a role in the regulation of bone metabolism.
 ...
PMID:Identification and cloning of human P2U purinoceptor present in osteoclastoma, bone, and osteoblasts. 748 91

The effects of the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3 (1,25D), are mediated via the vitamin D receptor (VDR). 1,25D is known to have profound effects on bone resorption, but proof that the human osteoclast expresses VDR in vivo is absent. Receptors have been demonstrated in osteoblasts, and it has been generally accepted that the effects of 1,25D on formed osteoclasts are mediated via osteoblasts. Using conventional riboprobe in situ hybridization, VDR transcripts were readily detectable in osteoblasts within sections taken from normal bone and several actively remodelling bone tissues, namely, Paget's disease, renal hyperparathyroidism, and healing fracture callus. However, VDR transcripts also appeared to be present at low levels within osteoclasts from two pagetic samples and two hyperparathyroid samples. To examine this latter finding further, we have used the novel technique of in situ-reverse transcriptase-polymerase chain reaction (IS-RT-PCR) for specific amplification and detection of VDR mRNA within sections taken from the same conditions described above, and also from osteoclastoma samples. As expected, VDR transcripts were amplified and detected in osteoblasts and marrow cells, but were also prominently found in osteoclasts at approximately 50% of the level detected in osteoblasts in normal bone and at 60% in the active bone tissues. This suggests that in addition to effects on osteoclast precursors and those mediated via osteoblasts, 1,25D could exert direct effects on the active bone resorbing cells in vivo.
 ...
PMID:Demonstration of vitamin D receptor transcripts in actively resorbing osteoclasts in bone sections. 872 84

Giant cell tumor of bone (GCT) is a generally benign, osteolytic neoplasm comprising stromal cells and osteoclast-like giant cells. The osteoclastic cells, which cause bony destruction, are thought to be recruited from normal monocytic pre-osteoclasts by stromal cell expression of the ligand for receptor activator of nuclear factor kappaB (RANKL). This model forms the foundation for clinical trials in GCTs of novel cancer therapeutics targeting RANKL. Using expression profiling, we identified both osteoblast and osteoclast signatures within GCTs, including key regulators of osteoclast differentiation and function such as RANKL, a C-type lectin, osteoprotegerin, and the wnt inhibitor SFRP4. After ex vivo generation of stromal- and osteoclast-enriched cultures, we unexpectedly found that RANKL mRNA and protein were more highly expressed in osteoclasts than in stromal cells, as determined by expression profiling, flow cytometry, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. The expression patterns of molecules implicated in signaling between stromal cells and monocytic osteoclast precursors were analyzed in both primary and fractionated GCTs. Finally, using array-based comparative genomic hybridization, neither GCTs nor the derived stromal cells demonstrated significant genomic gains or losses. These data raise questions regarding the role of RANKL in GCTs that may be relevant to the development of molecularly targeted therapeutics for this disease.
 ...
PMID:Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB. 1597 58

Giant cell tumor of bone (GCTB) is a skeletal neoplasm, a locally aggressive tumor that occasionally metastasizes to the lungs. To identify novel biomarkers associated with GCTB progression and metastasis, we performed a miRNA microarray on ten primary tumors of GCTB, of which five developed lung metastases and the rest remained metastasis-free. Between metastatic and non-metastatic GCTB, 12 miRNAs were differentially expressed (such as miR-136, miR-513a-5p, miR-494, miR-224, and miR-542-5p). A decreased level of miR-136 in metastatic versus non-metastatic GCTB was significantly confirmed by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) (p=0.04). To identify potential target genes for the differentially expressed miRNAs, we used three target prediction databases. Then, to functionally validate the potential target genes of the differentially expressed miRNAs, we re-analyzed our previous gene expression data from the same ten patients. Eight genes such as NFIB, TNC, and FLRT2 were inversely expressed relative to their predicted miRNA regulators. NFIB expression correlated in metastatic GCTB with no or low expression of miR-136, and this gene was selected for further verification with qRT-PCR and immunohistochemistry. Verification of NFIB mRNA and protein by qRT-PCR showed elevated expression levels in metastatic GCTBs. Further, the protein expression level of NFIB was tested in an independent validation cohort of 74 primary archival GCTB specimens. In the primary tumors that developed metastases compared to the disease-free group, NFIB protein was moderately to strongly expressed at a higher frequency. Thus, in GCTB, miR-136 and NFIB may serve as prognostic makers.
 ...
PMID:MicroRNA expression profiles in metastatic and non-metastatic giant cell tumor of bone. 2317 52