Response of human osteoblast-like cells to fluid flow shear: A potential role for the microtubule network and primary ciliums
Bibliographic record
Abstract
Introduction: A limited understanding of the cellular mechanisms governing bone mechanotransduction has inhibited the development of clinical treatments for a variety of bone disorders, including osteoporosis, osteoarthritis and microgravity-associated bone atrophy. The cytoskeleton is thought to play a role in cellular mechanotransduction, however the exact mechanism in bone cells has not yet been clearly elucidated. Studies involving cytoskeletal inhibitors have not generally considered secondary effects on cellular organelles such as the primary cilia. These cellular projections could account for the disparity between shear stresses predicted to occur in vivo and the minimum threshold of membrane deformation required to elicit a cellular response in vitro. Methods: MG-63 (human osteoblast-like) cells were cultured in vitro. Cultures were exposed to intermittent cyclic fluid flow shear stress (1 Pa amplitude), for 8 or 12 hrs. Some cultures were loaded in the presence of nocodazole (a microtubule inhibitor) or cytochalasin D (an actin filament inhibitor). The cellular response was analyzed through RT-PCR assessment of messenger RNA levels for specific molecules related to matrix metabolism. The effects of drug treatments on cytoskeletal disorganization and the primary cilia were assessed with immunocytochemistry and electron microscopy. Results: In untreated cultures, shear stress was associated with significant increases in mRNA levels for collagen I and matrix metalloproteinases 1 and 3, for both time points assessed. These increases were maintained in cultures loaded in the presence of cytochalasin D, but were almost completely abrogated in nocodazole-treated cultures. Cytoskeletal inhibitors exerted some dose-dependent effects on length and structure of primary cilia in MG-63 cells. Conclusions: The microtubule network appears to be necessary for some shear-induced responses of osteoblast-like cells. MG-63 cells possess primary cilia, organelles that could amplify fluid flow shear, accounting for some apparent contradictions between studies related to osteoblast mechanosensitivity. Since these structures are composed of microtubules, the observation that microtubule disruptors inhibit the shear response of osteoblast-like cells suggests the primary cilium may have a role in osteoblast mechanotransduction. The effects of cytoskeletal inhibitors on cilium structure may explain the conflicting results of earlier mechanotransduction studies.
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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) | 0.003 | 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".