Fluid Shear Stress Promotes Osteoblast Proliferation and Suppresses Mitochondrial-Mediated Osteoblast Apoptosis
1Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou Gansu, China.
Abstract:
MicroRNAs (miRNAs) play vital roles in bone metabolism and participate in the mechanically induced bone alterations. The underlying molecular mechanisms by which fluid shear stress (FSS) regulate the proliferative and apoptotic phenotypic changes of osteoblasts remain elusive. The study aimed to investigate the regulatory effects of FSS on osteoblast proliferative and apoptotic phenotypes and the roles of miR-214-3p-ATF4 (activating transcription factor 4) signaling axis in the mechanomodulation processes. FSS promoted the proliferative activity of osteoblasts and suppressed mitochondrial-mediated osteoblast apoptosis. FSS decreased miR-214-3p expression and increased ATF4 expression in MC3T3-E1 osteoblasts. MiR-214-3p inhibited osteoblast proliferative activity and promoted mitochondrial-mediated osteoblast apoptosis. Overexpression of miR-214-3p attenuated FSS-enhanced osteoblast proliferation and FSS-suppressed mitochondrial-mediated osteoblast apoptosis. We validated that ATF4 acted as a target gene of miR-214-3p. Moreover, miR-214 3p regulated osteoblast proliferation and apoptosis through targeting ATF4. Taken together, our study proved that FSS could suppress mitochondrial-mediated osteoblast apoptosis and promote osteoblast proliferation through the miR-214-3p-ATF4 signaling axis.
Insights
Fluid shear stress (FSS) promotes osteoblast proliferation and reduces apoptosis by downregulating miR-214-3p and upregulating activating transcription factor 4 (ATF4). This miR-214-3p-ATF4 axis mediates bone cell mechanotransduction.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Bone Biology
Background:
- MicroRNAs (miRNAs) are crucial regulators of bone metabolism and cellular responses to mechanical stimuli.
- The precise molecular mechanisms linking fluid shear stress (FSS) to osteoblast proliferation and apoptosis are not fully understood.
Purpose of the Study:
- To investigate the effects of FSS on osteoblast proliferation and apoptosis.
- To elucidate the role of the miR-214-3p-ATF4 signaling pathway in FSS-mediated osteoblast responses.
Main Methods:
- Exposure of MC3T3-E1 osteoblasts to FSS.
- Quantitative real-time PCR and Western blotting to measure miR-214-3p and ATF4 expression.
- Cell proliferation assays and apoptosis assays (e.g., mitochondrial-mediated apoptosis).
- MiR-214-3p mimic/inhibitor transfection and ATF4 knockdown/overexpression experiments.
Main Results:
- FSS significantly increased osteoblast proliferation and suppressed mitochondrial-mediated apoptosis.
- FSS exposure led to decreased miR-214-3p expression and increased ATF4 expression in osteoblasts.
- MiR-214-3p was found to inhibit osteoblast proliferation and promote apoptosis.
- Overexpression of miR-214-3p counteracted the effects of FSS on proliferation and apoptosis.
- ATF4 was confirmed as a direct target gene of miR-214-3p, mediating its effects on osteoblast phenotype.
Conclusions:
- FSS modulates osteoblast proliferation and apoptosis via the miR-214-3p-ATF4 signaling axis.
- This pathway is a key mediator of osteoblast mechanotransduction, influencing bone remodeling and adaptation.
- Targeting the miR-214-3p-ATF4 pathway may offer therapeutic strategies for bone diseases related to mechanical loading.
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