Fluid shear stress induces Runx‐2 expression via upregulation of PIEZO1 in MC3T3‐E1 cells

Abstract

Mechanically induced biological responses in bone cells involve a complex biophysical process. Although various mechanosensors have been identified, the precise mechanotransduction pathway remains poorly understood. PIEZO1 is a newly discovered mechanically activated ion channel in bone cells. This study aimed to explore the involvement of PIEZO1 in mechanical loading (fluid shear stress)‐induced signaling cascades that control osteogenesis. The results showed that fluid shear stress increased PIEZO1 expression in MC3T3‐E1 cells. The fluid shear stress elicited the key osteoblastic gene Runx‐2 expression; however, PIEZO1 silencing using small interference RNA blocked these effects. The AKT/GSK‐3β/β‐catenin pathway was activated in this process. PIEZO1 silencing impaired mechanically induced activation of the AKT/GSK‐3β/β‐catenin pathway. Therefore, the results demonstrated that MC3T3‐E1 osteoblasts required PIEZO1 to adapt to the external mechanical fluid shear stress, thereby inducing osteoblastic Runx‐2 gene expression, partly through the AKT/GSK‐3β/β‐catenin pathway.

Induction of osteogenic differentiation of bone marrow stromal cells on 3D polyester-based scaffolds solely by subphysiological fluidic stimulation in a laminar flow bioreactor

“…24,46,47 Hence, the results provide evidence that osteogenesis of BMSC on 3D non-osteoinductive scaffolds can be induced solely by fluid flow in the absence of osteogenic supplements as reported in 2D systems where fluid effect is purely represented as shear stress. 14,15,19,20 Various types of bioreactors have been developed for bone tissue engineering. Each of the systems has distinctive features, and therefore, the identification of experimental parameters is the first step in reconciling the experimental data.…”

“… 24 , 46 , 47 Hence, the results provide evidence that osteogenesis of BMSC on 3D non-osteoinductive scaffolds can be induced solely by fluid flow in the absence of osteogenic supplements as reported in 2D systems where fluid effect is purely represented as shear stress. 14 , 15 , 19 , 20 …”

“…For examples, as early as 1 h after perfusion, osteoblast precursors, MC3T3-E1, responded to shear stress at 2 Pa by upregulating a key transcription factor, Runt-related transcription factor 2 (RUNX2), for osteogenesis. 14 Further, the upregulation of other osteogenic markers such as collagen type 1 (COL1), osteocalcin (OCN) and alkaline phosphatase (ALP) was observed after 3 days of continuous perfusion. 15 Similarly, mesenchymal stem/stromal cells (MSC) were reported to undergo osteogenesis solely as a response to mechanical stimuli.…”

Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone

“…Meanwhile, Yoneda et al found that Piezo1 activator Yoda1 triggers Ca 2+ influx and promotes proliferation in MC3T3-E1 osteoblasts in vitro [ 82 ]. In vitro, MC3T3-E1 osteoblasts required Piezo1 to adapt to the external mechanical fluid shear stress, thereby inducing osteoblastic Runx2 (Runt-related transcription factor 2) gene expression, partly through the AKT/GSK-3β/β-catenin pathway [ 83 ]. Recently, Wang et al have found a Piezo1-YAP1-collagen pathway in osteoblasts in vivo and in vitro [ 8 ].…”

Mechanosensitive Piezo1 Channel Evoked-Mechanical Signals in Atherosclerosis

“…Different abnormalities or up/downregulation of cellular activities were observed in several studies following the silencing/blocking, deletion, cell specific or global knockout and deficiency of Piezo1. 9,[28][29][30][31][32][33] Since the recognition of Piezo1 &2 in 2010, they have been regarded as one of the most significant classes of mechanosensory proteins. It is now feasible to investigate the mechanism of Piezo1 engagement in physiological and pathophysiological processes as a result of recent developments in understanding their topology, the identification of the agonists Yoda1, Jedi1&2 as well as the antagonist GsMTx4, Ruthenium Red.…”