Targeted Inhibition of Osteopontin Expression in the Mammary Gland Causes Abnormal Morphogenesis and Lactation Deficiency
Bibliographic record
Abstract
Osteopontin (OPN) is a sialic acid-rich, adhesive, extracellular matrix (ECM) protein with Arg-Gly-Asp cell-binding sequence that interacts with several integrins, including alpha(v)beta(3). Since the ECM is a key regulator of mammary gland morphogenesis, and mammary epithelial cells express OPN at elevated levels, we sought to determine whether this protein plays a role in the postnatal mammary gland development. By generating transgenic mice that express OPN antisense-RNA (AS-OPN mice) in the mammary epithelia we achieved suppression of OPN production in this organ. The pregnant AS-OPN mice displayed a lack of mammary alveolar structures, a drastic reduction in the synthesis of beta-casein, whey acidic milk protein, and lactation deficiency. In agreement with these findings, we uncovered that a mammary cell line, NMuMG, which undergoes both structural and functional differentiation on ECM-coated plates, when transfected with an antisense OPN-cDNA construct, failed to undergo such differentiation. Furthermore, the results of gel-invasion assays demonstrated that these cells manifest elevated matrix metalloproteinase (MMP) activity when OPN expression is significantly reduced. The identity of this proteinase as MMP-2 is confirmed by Western blotting, zymography, and inhibition of its activity by a specific inhibitor, TIMP-2. Taken together, our results demonstrate, for the first time, an essential role of OPN in mammary gland differentiation and that the molecular mechanism(s) of its action, at least in part, involves down-regulation of MMP-2.
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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".