He Hu1, Chuanlong Zhao2, Peiguang Zhang3, Yalong Liu4, Yulian Jiang3, Enquan Wu1, Hao Xue3, Caiyun Liu5, Zhehai Li6. 1. Department of Orthopedics, The Inner Mongolia People's Hospital, Hohhot 010017, Inner Mongolia, PR.China. 2. Department of Orthopedics, Ordos Central Hospital, Ordos 017000, Inner Mongolia, PR.China. 3. Department of Orthopedics, The Third Affiliated Hospital, Inner Mongolia Medical University, Baotou, 014010, Inner Mongolia, PR.China. 4. Department of Orthopedics, Yangling, Demonstration Zone hospital District Hospital Xianyang 712100, Xian, PR.China. 5. Hunan Youcheng Biotechnology Co. Ltd, Changsha, 410000, China. 6. Department of Orthopedics, Beijing Northern Hospital, China North Industries, Beijing 100089, PR.China.; Inner Mongolia Medical University, Hohhot 014010, Inner Mongolia, PR.China.. Electronic address: lizhehai0472@126.com.
Abstract
BACKGROUNDS: Osteoactivin (OA) is a key regulator promoting bone marrow stromal cells osteogenesis progress, while Dexamethasone (Dex) could inhibit OA induced osteogenesis and lead to osteoporosis. miR-26b increased during BMSC osteogenesis but whether it participates in this progress is enigma. Osteogenesis is under regulation of canonical Wnt signaling pathway which could serve as potential target for miR-26b. It bears therapeutic potential if miR-26b could regulate osteogenesis and antagonize Dex induced Osteoporosis (OP). METHODS: BMSC were isolated from bone marrow of rats and induced for osteogenesis by OA administration. We detected miR-26b mRNA level together with osteogenesis related genes or Wnt signal pathway related genes by qRT-PCR. BMSC cells with miR-26b inhibitor or mimics revealed the effect of miR-26b on osteogenesis. The osteogenesis efficiency was detected by Alizarin Red staining and ALP activity. Protein level of canonical Wnt signal pathway and other proteins were detected by Western blot. The interaction between miR-26b and GSK3β was detected by dual luciferase reporter assay. RESULTS: We found that miR-26b was increased during OA induced BMSC osteogenesis. Inhibiting miR-26b could lead to osteogenesis inhibition while miR-26b mimics could promote this progress. The key regulator of Wnt signal pathway GSK3β is down-regulated when miR-26b was overexpressed, resulting in β-catenin activation. Since Dex could promote GSK3β expression and inhibit Wnt signal, miR-26b could also alleviate Dex induced osteogenesis inhibition. CONCLUSION: Our findings indicate that miR-26b promoted BMSC osteogenesis by directly targeting GSK3β and activating canonical Wnt signal pathway, suggesting miR-26b might be serve as potential therapeutic candidate of osteoporosis.
BACKGROUNDS: Osteoactivin (OA) is a key regulator promoting bone marrow stromal cells osteogenesis progress, while Dexamethasone (Dex) could inhibit OA induced osteogenesis and lead to osteoporosis. miR-26b increased during BMSC osteogenesis but whether it participates in this progress is enigma. Osteogenesis is under regulation of canonical Wnt signaling pathway which could serve as potential target for miR-26b. It bears therapeutic potential if miR-26b could regulate osteogenesis and antagonize Dex induced Osteoporosis (OP). METHODS: BMSC were isolated from bone marrow of rats and induced for osteogenesis by OA administration. We detected miR-26b mRNA level together with osteogenesis related genes or Wnt signal pathway related genes by qRT-PCR. BMSC cells with miR-26b inhibitor or mimics revealed the effect of miR-26b on osteogenesis. The osteogenesis efficiency was detected by Alizarin Red staining and ALP activity. Protein level of canonical Wnt signal pathway and other proteins were detected by Western blot. The interaction between miR-26b and GSK3β was detected by dual luciferase reporter assay. RESULTS: We found that miR-26b was increased during OA induced BMSC osteogenesis. Inhibiting miR-26b could lead to osteogenesis inhibition while miR-26b mimics could promote this progress. The key regulator of Wnt signal pathway GSK3β is down-regulated when miR-26b was overexpressed, resulting in β-catenin activation. Since Dex could promote GSK3β expression and inhibit Wnt signal, miR-26b could also alleviate Dex induced osteogenesis inhibition. CONCLUSION: Our findings indicate that miR-26b promoted BMSC osteogenesis by directly targeting GSK3β and activating canonical Wnt signal pathway, suggesting miR-26b might be serve as potential therapeutic candidate of osteoporosis.
Authors: Chiara Mazziotta; Carmen Lanzillotti; Maria Rosa Iaquinta; Francesca Taraballi; Elena Torreggiani; John Charles Rotondo; Lucia Otòn-Gonzalez; Elisa Mazzoni; Francesca Frontini; Ilaria Bononi; Monica De Mattei; Mauro Tognon; Fernanda Martini Journal: Int J Mol Sci Date: 2021-02-27 Impact factor: 6.208
Authors: Tomasz P Lehmann; Urszula Guderska; Klaudia Kałek; Maria Marzec; Agnieszka Urbanek; Alicja Czernikiewicz; Maria Sąsiadek; Paweł Karpiński; Andrzej Pławski; Maciej Głowacki; Paweł P Jagodziński Journal: Int J Mol Sci Date: 2021-12-22 Impact factor: 5.923