OR36-07 Sex-Specific Role of Preosteoclast-derived PDGF-BB in Preventing Glucocorticoid-Induced Type H Vessel Loss in Young Mice
Bibliographic record
Abstract
Abstract Disclosure: S.K. Barik: None. A. Otte: None. E. Zhang: None. J.L. Crane: None. The benefits of glucocorticoids (GCs) are negated by the detrimental effects on the skeleton, namely osteoporosis, osteonecrosis, and impaired growth. A unifying pathohistological feature of these osteotoxic effects are a reduction in bone vasculature. Type H blood vessels, identified by high expression of Endomucin (Emcnhi) and Pecam-1 (CD31hi) couple skeletal angiogenesis to osteogenesis. We have previously found that platelet-derived growth factor-BB (PDGF-BB) secretion from preosteoclasts (POCs) promoted Type H vessel formation and was inhibited by excessive, chronic GC exposure in young mice. In this study, we hypothesized that transgenic PDGF-BB overexpression in mice (PdgfbcTG), driven by a tartrate-resistant acid phosphatase promoter, would mitigate GC-induced reduction of Type H vessels and enhance skeletal angiogenesis. Wild-type (WT) and PdgfbcTG mice were injected daily with vehicle (Veh) or methylprednisolone (MPS) intraperitoneally for 4-weeks starting at postnatal day 14. Vessel phenotype in the distal femur metaphysis was analyzed using Emcn/CD31 co-immunofluorescence staining, followed by 3D vessel mapping and quantification in IMARIS. Overall, WT male mice had increased Type H vessel (Emcnhi and CD31hi) volume relative to WT females. Both sexes displayed decreased Type H vessel volume in response to MPS, which was abrogated by PDGF-BB overexpression by increasing mean vessel diameter in both sexes and vessel length only in males. During angiogenesis, endothelial cells either branch off from existing vessels or sprout from the end of existing vessels, thus we further investigated these characteristics in Emcn+ microvasculature. The orientation and straightness of the Emcn+ vessel branches were altered by MPS in WT mice, which was attenuated by PDGF-BB overexpression relative to Veh controls in both sexes. There was no change in the number of branch points. We observed a sex-specific effect of MPS on Emcn+ vessel sprouting. In males, MPS decreased Emcn+ sprouting vessel volume, length, and mean diameter, all of which were rescued by PDGF-BB overexpression. In females, MPS did not affect Emcn+ sprouting vessels. PDGF-BB overexpression increased Emcn+ sprouting vessel length and mean diameter relative to WT mice, and MPS further increased the vessel length but decreased diameter relative to PdgfbcTG Veh mice. The results suggest that the negative effect of GCs on angiogenesis and Type H vessel formation are through alterations in vessel branching in both sexes and sprouting only in males. PDGF-BB overexpression promoted Type H vessel maturation and helped attenuate the negative effect of GCs on bone vasculature. Additional studies are necessary to understand the sex-specific differences of how GCs and PDGF-BB affect directional growth or guidance signals during skeletal angiogenesis. Presentation: Monday, July 14, 2025
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 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".