Piezo1-mediated fluid shear stress promotes OPG and inhibits RANKL via NOTCH3 in MLO-Y4 osteocytes

ABSTRACT

Piezo1, a mechanosensitive ion channel, participates in a variety of biological processes in maintaining bone homeostasis. As the most abundant cells in bones of the mammals, osteocytes play an essential role in bone formation, remodeling, and bone mass maintenance. Here, by exposing MLO-Y4 osteocytes to the fluid shear stress (FSS) microenvironment, we explored the effect of Piezo1-mediated FSS on the expression of the molecules critical to the process of bone formation and resorption, Receptor Activator of Nuclear Factor-Kappa-B Ligand (RANKL) and Osteoprotegerin (OPG). It was found that 9 dyne/cm² loading for 30 minutes showed an upregulation trend on Piezo1 when MLO-Y4 osteocytes were exposed to an FSS microenvironment. FSS promotes the expression of OPG and inhibits the expression of RANKL. The blocker of Piezo1, GsMTx4, downregulates the effect of FSS on the expression of these two molecules. In addition, NOTCH3 was involved in this process. Thus, the results demonstrated that Piezo1-mediated FSS promotes the expression of OPG and inhibits the expression of RANKL via NOTCH3 in MLO-Y4 osteocytes.

KEYWORDS:

• Fluid shear stress
• Piezo1
• NOTCH3
• RANKL
• OPG
• osteocyte

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, [Y.X., or J.J.], upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19336950.2022.2085379

Additional information

Funding

The National Natural Science Foundation of China (81874017, 81960403 and 82060405, 82160422); Natural Science Foundation of Gansu Province of China (21JR7RA393); Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital (CY2017-ZD02, CY2021-MS-A07 and CY2021-MS-B02).