The adaptor protein 3BP2/SH3BP2 is required for RANKL‐induced osteoclastogenesis in RAW264.7 cells
Bibliographic record
Abstract
The adaptor protein (Abl SH3 binding protein‐2), a partner of Src and Syk kinases families, has been involved in leukocyte signaling and activation. Recently, genetic studies have associated mutations of 3BP2 gene with the human bone disease cherubism and with inflammation and bone dysfunction in mouse. Here the role of 3BP2 in osteoclast differentiation was investigated. Using stable extinction of 3BP2 expression in the RAW264.7 monocyte/macrophage cell line, we show that 3BP2 is required for RANKL‐induced differentiation of RAW264.7 cells into multinucleated TRAP+ osteoclasts, but not for GM‐CSF/IL4‐induced differentiation into dendritic cells. The absence of 3BP2 in RAW264.7 cells is associated with reduced actin cytoskeleton organization and impaired RANKL‐induced cell motility and fusion, and activation of IKK, ERK, JNK, but not of p38. In addition, we found a dramatic decrease of NFATc1, AP‐1 and NFkB transcription factors activities induced by RANKL stimulation, as well as a deregulated expression of multiple genes involved in early events controlling osteoclastogenesis, including NFATc1, c‐fos, beta3 integrin subunit, and several chemokine and chemoreceptor genes. Together, these data define the adaptor protein as a critical effector of multiple RANKL‐dependent signal transduction pathways involved in osteoclast differentiation. This work was supported by INSERM and ANR‐MRAR.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".