Longitudinal Analysis of Mesenchymal Progenitors and Bone Quality in the Stem Cell Antigen-1–Null Osteoporotic Mouse
Bibliographic record
Abstract
UNLABELLED: We performed a longitudinal analysis of bone quality in Sca-1-null mice. A tight temporal, site-specific association between Sca-1-deficient BMD deficiency and reduced mesenchymal progenitor frequency was observed. Defects in trabecular microarchitecture and mineralization were, at least partially, responsible for the age-related reduction in toughness of Sca-1(-/-) bones. INTRODUCTION: We previously showed that stem cell antigen 1 (Sca-1)-null mice undergo normal bone development but exhibit significantly decreased bone mass characteristic of age-dependent osteoporosis. The objective of this study was to characterize the initiation and progression of the Sca-1 mutant skeletal phenotype at the cellular, structural, material, and mechanical levels. MATERIALS AND METHODS: Sca-1-null and control mice were analyzed at 3, 5, 7, and 9 mo of age. In vitro osteoclastogenesis of bone marrow and spleen-derived progenitor populations was assessed. Bone marrow-derived mesenchymal progenitor frequency, along with osteogenic and adipogenic differentiation potential, was analyzed in vitro. Static histomorphometry of the sixth lumbar vertebrae was performed. Whole body, femoral, and vertebral BMD were assessed using DXA. Lumbar vertebrae were analyzed using microCT, back-scattered electron imaging, and compression tests. Three-point bending and femoral neck fracture tests were performed on excised femurs. RESULTS: Sca-1-null mice displayed an age-dependent, cell-autonomous osteoclast deficiency in vitro. From 7 mo of age onward, reduced Sca-1-null femoral BMD was observed alongside reduced mesenchymal progenitor frequency, and decreased in vitro osteogenic and adipogenic differentiation potential. Sca-1-deficient mice exhibited reduced whole body BMD compared with controls at all time-points analyzed. Although no differences in spinal BMD were observed, Sca-1(-/-) vertebrae exhibited decreased bone formation, with a maximal difference at 7 mo of age, inferior trabecular microarchitecture, and a greater degree of mineralization. At all sites tested, Sca-1-null bones exhibited reduced energy to failure from 5 mo onward. CONCLUSIONS: We showed a tight association within Sca-1-null mice between the initiation of stem cell defects and the exacerbation of deficiencies in bone quality at two sites clinically relevant to developing osteoporotic fractures. Sca-1-deficient mice, therefore, provide a novel and useful murine model of age-related osteoporosis, which with additional study, should further our understanding of the mechanisms underlying this increasingly prevalent disease.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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".