Follicle-Stimulating Hormone Does Not Impact RANKL-Induced Osteoclastogenesis
Bibliographic record
Abstract
Abstract Postmenopausal osteoporosis has been attributed to decreased estradiol levels. In the hypothalamic-pituitary-gonadal axis, estradiol synthesis is stimulated by follicle-stimulating hormone (FSH). FSH is secreted from the anterior pituitary gland and estradiol feeds back to the hypothalamus and pituitary to suppress FSH production. In postmenopausal women, the loss of estradiol (and inhibin) negative feedback leads to elevated serum FSH levels. It was recently proposed that this increase in FSH also contributes to postmenopausal osteoporosis by stimulating differentiation and activation of bone-resorbing osteoclast cells. Our objectives were to determine whether FSH has direct actions on osteoclast differentiation in vitro and, if so, its mechanism(s) of action. First, a murine leukemic monocyte/macrophage cell line, RAW264.7, was differentiated into osteoclasts by treatment with receptor activator of nuclear factor kappa-B ligand (RANKL, 50 ng/mL) for seven days. As expected, we observed the appearance of osteoclasts, characterized as tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. RANKL also induced expression of established osteoclast differentiation markers, including Trap, cathepsin K (Ctsk), and matrix metalloproteinase-9 (Mmp9). The mRNA expression of FSH receptor (Fshr), however, was low to undetectable both before and after osteoclast differentiation. Co-treatment of RAW264.7 cells with FSH (35, 70 and 140 IU/L) and RANKL did not further impact the expression of Rank, Trap, Ctsk, Mmp-9, or Fshr. Second, primary murine monocytes were differentiated into osteoclasts by treatment with RANKL (50 ng/mL) and macrophage colony-stimulating factor (M-CSF, 25 ng/mL) for five days. FSH co-treatment (70 and 140 IU/L) had no impact on the expression of osteoclast markers, and Fshr expression was low to undetectable both before and after osteoclast differentiation, consistent with the results from RAW264.7 cells. In conclusion, in our hands, FSH does not impact RANKL-induced osteoclast differentiation in immortalized or primary murine monocytes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".