β<sub>2</sub>‐adrenergic receptors expressed on murine chondrocytes stimulate cellular growth and inhibit the expression of Indian hedgehog and collagen type X
Bibliographic record
Abstract
The sympathetic nervous system has been demonstrated to have a role in regulating bone remodeling through beta-adrenergic receptors (beta-AR) expressed on osteoblasts. Studies using beta(2)-adrenergic receptor agonists in vivo have also suggested an effect on endochondral bone development; however, it was not clear if this effect was mediated through osteoblasts or chondrocytes. To more thoroughly examine the role of beta-AR in chondrocytes we characterized the expression and signal transduction systems activated by beta-AR in growth plate chondrocytes prepared from ribs of embryonic E18.5 mice. Using RT-PCR and immunohistochemistry we found that the chondrocytes expressed only beta(2)-AR. The receptors were coupled to stimulation of adenylyl cyclase, phosphorylation of the cyclic AMP response element binding protein (CREB) and extracellular signal-regulated kinase (ERK1/2). Stimulation of ERK1/2 was transient and limited by the concomitant stimulation of the mitogen-activated protein kinase phosphatase (MKP-1). Isoproterenol stimulated the growth of chondrocytes as assessed by increased incorporation of [(3)H]-thymidine into the cells. The cellular expression of two markers of chondrocyte differentiation, Indian hedgehog, expressed in pre-hypertrophic cells and collagen type X, expressed in hypertrophic chondrocytes, were both significantly inhibited after incubation with isoproterenol. Collectively, these findings demonstrate regulation of chondrocytes through beta(2)-AR expressed on the cells that stimulate their growth and inhibit their differentiation, indicating that the sympathetic nervous system may be an important regulator of embryonic cartilage development.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".