How Endothelin A Receptor Affects Bone Formation
Author Information
Author(s): Clines Gregory A, Mohammad Khalid S, Grunda Jessica M, Clines Katrina L, Niewolna Maria, McKenna C Ryan, McKibbin Christopher R, Yanagisawa Masashi, Suva Larry J, Chirgwin John M, Guise Theresa A
Primary Institution: University of Alabama at Birmingham
Hypothesis
We hypothesized that sex steroids modulate endothelin signaling and tested the effects of gonadectomy.
Conclusion
Endothelin signaling in osteoblasts is an important regulator of postnatal trabecular bone remodeling and a modulator of androgen effects on bone.
Supporting Evidence
- ETAR was inactivated in osteoblasts by crossing ETAR-floxed and osteocalcin-Cre mice.
- Tibial trabecular bone volume was significantly lower from 12 weeks in KO versus WT mice.
- Bone-formation rate, osteoblast density, and in vitro osteoblast differentiation were reduced by targeted inactivation of ETAR.
- Male mice castrated at 8 weeks of age showed reduced rates of tibial and femoral BMD acquisition compared with WT mice.
Takeaway
This study shows that a protein called endothelin helps bones grow and change, especially when combined with hormones like testosterone.
Methodology
Histomorphometric analyses were performed on osteoblast-targeted ETAR knockout and wild-type mice, examining bone volume and density.
Potential Biases
Potential bias in the selection of animal models and the interpretation of results based on sex differences.
Limitations
The study primarily focused on male and female mice, which may not fully represent human bone metabolism.
Participant Demographics
Male and female mice aged 4, 8, 12, and 64 weeks.
Statistical Information
P-Value
0.025
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website