Loss of Tyrosine Phosphatase Mu Promotes Scoliosis Progression Through Osteopontin-α5β1 Integrin Signaling and PIPK1γ90 Activity
Bibliographic record
Abstract
Adolescent idiopathic scoliosis (AIS) is characterized by a curvature of the spine affecting approximately 4% of the pediatric population, and the mechanisms driving its progression remain poorly understood. Whole-exome sequencing of a French-Canadian AIS cohort with severe scoliosis identified rare variants in the PTPRM gene, which encodes Protein Tyrosine Phosphatase μ (PTPµ). However, these rare variants alone did not account for the pronounced reduction in PTPµ at both mRNA and protein levels in severe AIS cases. This led us to investigate epigenetic regulators and the identification of five microRNAs (miR-103a-3p, miR-107, miR-148a-3p, miR-148b-3p, and miR-152-3p) that target PTPRM mRNA. These microRNAs were significantly elevated in plasma from severe AIS patients, and miR-148b-3p was also upregulated in AIS osteoblasts. Phenotypic analysis of bipedal Ptrprm knockout (PTPµ −/−) mice showed increased prevalence and severity of scoliosis, while quadrupedal PTPµ −/− mice did not develop scoliosis, underscoring PTPµ’s role as a disease-modifying factor. Mechanistically, PTPµ deficiency was found to disrupt Gi-coupled receptor signaling in osteoblasts by enhancing the interaction between osteopontin (OPN) and α5β1 integrin, along with increased tyrosine phosphorylation of phosphatidylinositol-4-phosphate 5-kinase type I (PIPKIγ90). These findings provide novel insights into the molecular mechanisms underlying spinal deformity progression in AIS, linking PTPµ depletion to aberrant OPN-α5β1 integrin signaling and highlighting potential therapeutic targets to stop, mitigate, or prevent scoliosis.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".