P2 nucleotide receptors in osteoclasts
Bibliographic record
Abstract
Abstract Osteoclasts are large, multinucleated cells responsible for the resorption of bone and other mineralized tissues. Whereas low concentrations of extracellular ATP stimulate osteoclast formation and resorptive activity, high concentrations inhibit osteoclast formation. Cell surface receptors for nucleotides are classified into two families—P2X (ligand‐gated channels nonselective for cations) and P2Y (G‐protein‐coupled receptors linked, in most cases, to release of Ca2+ from intracellular stores). Several subtypes of P2 receptors are expressed by mammalian osteoclasts. The P2X4 receptor has been identified at both protein and messenger RNA levels and ATP activates a nonselective cation current with properties similar to that mediated by the cloned P2X4 channel. The P2X2 receptor is also expressed; however, currents with properties of P2X2 have yet to be identified. Functional and expression studies also support the existence of the P2X7 receptor, which is activated by high concentrations of ATP. Application of nucleotides to osteoclasts elicits transient elevation of cytosolic free Ca2+ concentration and activation of Ca2+‐dependent K+ channels. Both these responses are mediated, at least in part, by release of Ca2+ from intracellular stores, consistent with the presence of functional P2Y receptors. Expression of P2Y1 and P2Y2 receptors has been demonstrated in mammalian osteoclasts. The presence of multiple subtypes of P2 receptors may account for the biphasic effects of extracellular nucleotides on osteoclast function. These receptors represent potential targets for the development of novel therapeutics to inhibit bone resorption in diseases such as rheumatoid arthritis, osteoporosis, tumor‐induced osteolysis, and periodontitis. Drug Dev. Res. 53:130–139, 2001. © 2001 Wiley‐Liss, Inc.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".