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Record W7132963286

Osteocyte Form and Function in Loading and Unloading Environments

2021· dissertation· W7132963286 on OpenAlexaff
Roxanne Fournier

Bibliographic record

VenueTSpace · 2021
Typedissertation
Language
FieldMedicine
TopicSpaceflight effects on biology
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsOsteocyteMechanosensitive channelsCell cultureSuspension (topology)ScaffoldMechanotransductionWeightlessnessRANKLMechanosensation
DOInot available

Abstract

fetched live from OpenAlex

Long-term human spaceflight presents unprecedented challenges to the human body, such as microgravity-induced bone loss. Without intervention, astronauts lose between 1 – 2% bone mineral density per month in weight bearing bones and the cellular mechanisms involved in this process are still poorly understood. To date, the most abundant cell of bone, the osteocyte, has rarely been subjected to spaceflight. Yet osteocytes are known to be important regulators of bone loss in immobilized and elderly people. The first objective of this thesis was to develop novel 3D culture methods to study osteocytes using the Rotary Cell Culture System (RCCS). This device is commonly used for both suspension culture and simulated microgravity by clinorotation. The second objective was to investigate morphological and gene expression changes in MLO-Y4 cells following suspension culture or clinorotation. We found that the ideal 3D scaffold consisted of 2% type I collagen mixed with 6% synthetic hydroxyapatite (collagen-HA). The scaffold was successfully formed into droplets for suspension culture, whereas it was adhered to the RCCS vessel walls for clinorotation. After 3 days of suspension culture, MLO-Y4 cells embedded in the collagen-HA droplets showed reduced expression of the mechanosensitive genes DMP1, E11, IL-6, and RANKL and the number of cells was elevated compared to the static control. We estimated that the drag force acting on the aggregate of droplets was in the range of 2.1 – 4.4 dynes/cm2, speculated to provide a small but significant stimulatory effect on the cells located on the surface, which may de-sensitize them over the course of 3 days. Following clinorotation for 3 days, MLO-Y4 cells showed reduced expression of DMP1 and E11 genes while the cell number was unchanged compared to the static control. Since clinorotation and spaceflight cause the de-differentiation of other bone cells, we speculated that our MLO-Y4 cells were also de-differentiating during clinorotation, resulting in the lower expression of osteocyte-specific genes.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.631
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.013
GPT teacher head0.304
Teacher spread0.291 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2021
Admission routes1
Has abstractyes

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