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 mitochondrialmediated 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.
This mini-review aims to introduce the association between Secretory clusterin/apolipoprotein J (sCLU) and diverse musculoskeletal diseases. A comprehensive review of the literature was performed to identify basic science and clinical studies, which implied the therapeutic and prognostic role of sCLU in diverse musculoskeletal diseases. sCLU is a multifunctional glycoprotein that is ubiquitously expressed in various tissues and is implicated in many pathophysiological processes. Dysregulated expression of sCLU had been reported to be assocaited with proliferative or apoptotic molecular processes and inflammatory responses, which participated in many pathophysiological processes such as degenerative musculoskeletal diseases including ischemic osteonecrosis, osteoarthritis (OA) and degenerative cervical myelopathy (spinal cord injury), neoplastic musculoskeletal diseases, inflammatory and autoimmune musculoskeletal diseases including Rheumatoid arthritis (RA), joint damage induced by Brucella abortus, Sjogren's syndrome, idiopathic inflammatory myopathies, muscle glucose metabolism, insulin sensitivity and traumatic musculoskeletal diseases. Recent findings of sCLU in these musculoskeletal diseases provides insights on the therapeutic and prognostic role of sCLU in these musculoskeletal diseases. sCLU may serve as a promising therapeutic target for ischemic osteonecrosis, OA and spinal cord injury as well as a potential prognostic biomarker for OA and RA. Moreover, sCLU could act as a prognostic biomarker for osteosarcoma (OS) and a promising therapeutic target for OS resistance. Although many studies support the potential therapeutic and prognostic role of sCLU in some inflammatory and autoimmune-mediated musculoskeletal diseases, more future researches are needed to explore the molecular pathogenic mechanism mediated by sCLU implied in these musculoskeletal diseases.