Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity.
Sci Adv
; 5(9): eaau7802, 2019 09.
Article
in En
| MEDLINE
| ID: mdl-31579816
ABSTRACT
Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading-mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas-NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stress, Mechanical
/
Bone and Bones
/
Signal Transduction
/
NF-kappa B
/
Crk-Associated Substrate Protein
/
Homeostasis
Limits:
Animals
Language:
En
Journal:
Sci Adv
Year:
2019
Document type:
Article
Affiliation country:
Japan