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The Role of PTHrP in Osteoblast Response to Microgravity: Implications for Osteoporosis Development.

Metadata Updated: December 6, 2023

Prolonged skeletal unloading through bedrest results in bone loss similar to that observed in elderly osteoporotic patients but with an accelerated timeframe. This rapid effect on weight-bearing bones is also observed in astronauts who lose up to 2% of their bone mass per month spent in Space. Despite important implications for Spaceflight travellers and bedridden patients on Earth the exact mechanisms involved in disuse osteoporosis have not been elucidated. Parathyroid hormone-related protein (PTHrP) regulates many physiological processes including skeletal development and has been proposed as a gravisensor. To investigate the role of PTHrP in microgravity-induced bone loss trabecular osteoblasts (TOs) from Pthrp+/+ and -/- mice were exposed to simulated microgravity for 6 days. Viability of TOs decreased in inverse proportion to PTHrP expression levels. Microarray analysis of Pthrp+/+ TOs after 6 days at 0g revealed expression changes in genes encoding prolactins,apoptosis and survival molecules bone metabolism and extra-cellular matrix composition proteins chemokines IGF family and Wnt-related signalling molecules. Importantly 88% of 0g-induced expression changes in Pthrp+/+ cells overlap those observed in Pthrp-/- cells in normal gravity. Pulsatile treatment with PTHrP1-36 peptide during microgravity exposure reversed a large proportion of 0g-induced changes in Pthrp+/+ TOs. Our results confirm PTHrP efficacy as an anabolic agent to prevent microgravity-induced cell death in TOs. Total RNA samples extracted from Pthrp+/+and -/- trabecular osteoblasts (TOs) exposed for 6 days to simulated 0g in Synthecon rotating cell or left 6 days in culture at 1g. Cells had either been treated with a pulsatile treatment (2 h/day) of PTHrP1-36 peptide (10-8M) or received a change in growth medium. In total: 8 different conditions with 2 replicates each i.e. Pthrp+/+ TOs at 0g or 1g with or without PTHrP1-36 treatment and Pthrp-/- TOs at 0g or 1 g,with or without PTHrP1-36 treatment.

Access & Use Information

Public: This dataset is intended for public access and use. License: No license information was provided. If this work was prepared by an officer or employee of the United States government as part of that person's official duties it is considered a U.S. Government Work.

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Dates

Metadata Created Date January 31, 2023
Metadata Updated Date December 6, 2023
Data Update Frequency irregular

Metadata Source

Harvested from NASA Data.json

Additional Metadata

Resource Type Dataset
Metadata Created Date January 31, 2023
Metadata Updated Date December 6, 2023
Publisher National Aeronautics and Space Administration
Maintainer
Identifier nasa_genelab_GLDS-107_a3s4-zqy3
Data First Published 2018-09-05
Data Last Modified 2023-01-26
Category Earth Science
Public Access Level public
Data Update Frequency irregular
Bureau Code 026:00
Metadata Context https://project-open-data.cio.gov/v1.1/schema/catalog.jsonld
Metadata Catalog ID https://data.nasa.gov/data.json
Schema Version https://project-open-data.cio.gov/v1.1/schema
Catalog Describedby https://project-open-data.cio.gov/v1.1/schema/catalog.json
Harvest Object Id 6b69ddc8-e4fe-4751-9c68-84df3d478c5d
Harvest Source Id 58f92550-7a01-4f00-b1b2-8dc953bd598f
Harvest Source Title NASA Data.json
Homepage URL https://data.nasa.gov/d/a3s4-zqy3
Program Code 026:005
Source Datajson Identifier True
Source Hash b1b203ffc4b13c2748802967dc53acd8001e128a664fc3f7e141e3dbabcd4ed8
Source Schema Version 1.1

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