miR‑205 regulates bone turnover in elderly female patients with type 2 diabetes mellitus through targeted inhibition of Runx2

Zhang,Guangfeng; Li,Huafeng; Zhao,Wenjie; Li,Min; Tian,Linlin; Ju,Wenwen; Li,Xiaobing

doi:10.3892/etm.2020.8867

miR‑205 regulates bone turnover in elderly female patients with type 2 diabetes mellitus through targeted inhibition of Runx2

Authors:
- Guangfeng Zhang
- Huafeng Li
- Wenjie Zhao
- Min Li
- Linlin Tian
- Wenwen Ju
- Xiaobing Li
View Affiliations

Affiliations: Department of MRI, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161099, P.R. China, Department of Endocrinology (I), The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161099, P.R. China
Published online on: June 10, 2020 https://doi.org/10.3892/etm.2020.8867
Pages: 1557-1565
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to explore the expression of microribonucleic acid (microRNA) (miR)‑205 in bone tissues and serum of elderly female patients with type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP), and to investigate the effect of miR‑205 on osteogenesis/adipogenesis of bone marrow mesenchymal stem cells (BMSCs) and its mechanism in elderly female mice with T2DM + OP. The bone tissues and serum of 24 female patients with T2DM + OP at the Third Affiliated Hospital of Qiqihar Medical University were collected as the research group, while those of 24 healthy people were collected as the control group. The expression level of miR‑205 was detected in both groups via reverse transcription‑polymerase chain reaction (RT‑PCR). Then the elderly female mouse model of T2DM + OP was established as a model group, while normal mice of the same age were used as the control group. The mice in the model and control groups were transfected with miR‑205 mimic, negative control (NC)‑mimic, miR‑205‑inhibitor and NC‑inhibitor. Alizarin red S (ARS) staining and RT‑PCR were conducted after osteogenic induction for 21 days, and oil red O (ORO) staining and RT‑PCR were performed after adipogenic induction for 24 days. The overexpression of miR‑205 inhibited osteogenic differentiation and promoted adipogenic differentiation of BMSCs in elderly female mice with T2DM + OP, while knockdown of miR‑205 promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs in elderly female mice with T2DM + OP. In addition, miR‑205 was able to directly suppress the expression of its target gene RUNX family transcription factor 2 (Runx2). The expression level of miR‑205 was obviously increased in female patients with T2DM + OP and the elderly female mouse model of T2DM + OP. In addition, miR‑205 was able to regulate the osteogenic/adipogenic differentiation of BMSCs, and miR‑205/Runx2 may be a new method and target for the treatment of female patients with T2DM + OP.

View Figures

View References

1	Picke AK, Campbell G, Napoli N, Hofbauer LC and Rauner M: Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Endocr Connect. 8:R55–R70. 2019.PubMed/NCBI View Article : Google Scholar
2	Liu M, Lu Y, Cheng X, Ma L, Miao X, Li N, Sun B, Yan S, Li J and Li C: Relationship between abnormal glucose metabolism and osteoporosis in Han Chinese men over the age of 50 years. Clin Interv Aging. 14:445–451. 2019.PubMed/NCBI View Article : Google Scholar
3	Chen FP, Kuo SF, Lin YC, Fan CM and Chen JF: Status of bone strength and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes. Menopause. 26:182–188. 2019.PubMed/NCBI View Article : Google Scholar
4	Pagnotti GM, Styner M, Uzer G, Patel VS, Wright LE, Ness KK, Guise TA, Rubin J and Rubin CT: Combating osteoporosis and obesity with exercise: Leveraging cell mechanosensitivity. Nat Rev Endocrinol. 15:339–355. 2019.PubMed/NCBI View Article : Google Scholar
5	Schepper JD, Irwin R, Kang J, Dagenais K, Lemon T, Shinouskis A, Parameswaran N and McCabe LR: Probiotics in Gut-bone signaling. Adv Exp Med Biol. 1033:225–247. 2017.PubMed/NCBI View Article : Google Scholar
6	Rizzo S, Farlay D, Akhter M, Boskey A, Recker R, Lappe J and Boivin G: Variables reflecting the mineralization of bone tissue from fracturing versus nonfracturing postmenopausal nonosteoporotic Women. JBMR Plus. 2:323–327. 2018.PubMed/NCBI View Article : Google Scholar
7	Hadjiargyrou M and Komatsu DE: The therapeutic potential of microRNAs as orthobiologics for skeletal fractures. J Bone Miner Res. 34:797–809. 2019.PubMed/NCBI View Article : Google Scholar
8	Pan BL, Tong ZW, Li SD, Wu L, Liao JL, Yang YX, Li HH, Dai YJ, Li JE and Pan L: Decreased microRNA-182-5p helps alendronate promote osteoblast proliferation and differentiation in osteoporosis via the Rap1/MAPK pathway. Biosci Rep. 38(pii: BSR20180696)2018.PubMed/NCBI View Article : Google Scholar
9	Cui Q, Xing J, Yu M, Wang Y, Xu J, Gu Y, Nan X, Ma W, Liu H and Zhao H: Mmu-miR-185 depletion promotes osteogenic differentiation and suppresses bone loss in osteoporosis through the Bgn-mediated BMP/Smad pathway. Cell Death Dis. 10(172)2019.PubMed/NCBI View Article : Google Scholar
10	Li H, Fan J, Fan L, Li T, Yang Y, Xu H, Deng L, Li J, Li T, Weng X, et al: MiRNA-10b reciprocally stimulates osteogenesis and inhibits adipogenesis partly through the TGF-β/SMAD2 signaling pathway. Aging Dis. 9:1058–1073. 2018.PubMed/NCBI View Article : Google Scholar
11	Li X, Ning L, Zhao X and Wan S: MicroRNA-543 promotes ovariectomy-induced osteoporosis through inhibition of AKT/p38 MAPK signaling pathway by targeting YAF2. J Cell Biochem: Dec 2, 2018 doi: 10.1002/jcb.28143 (Epub ahead of print).
12	Kim BJ, Lee JY, Park SJ, Lee SH, Kim SJ, Yoo HJ, Rivera De Pena SI, McGee-Lawrence M, Isales CM, Koh JM and Hamrick MW: Elevated ceramides 18:0 and 24:1 with aging are associated with hip fracture risk through increased bone resorption. Aging (Albany NY). 11:9388–9404. 2019.PubMed/NCBI View Article : Google Scholar
13	Sun Y, Xiong Y, Yan C, Chen L, Chen D, Mi B and Liu G: Downregulation of microRNA-16-5p accelerates fracture healing by promoting proliferation and inhibiting apoptosis of osteoblasts in patients with traumatic brain injury. Am J Transl Res. 11:4746–4760. 2019.PubMed/NCBI
14	Lozano Calderón SA, Garbutt C, Kim J, Lietz CE, Chen YL, Bernstein K, Chebib I, Nielsen GP, Deshpande V, Rubio R, et al: Clinical and molecular analysis of pathologic fracture-associated osteosarcoma: MicroRNA profile Is different and correlates with prognosis. Clin Orthop Relat Res. 477:2114–2126. 2019.PubMed/NCBI View Article : Google Scholar
15	Wang Y, Chen H and Zhang H: Tanshinone IIA exerts beneficial effects on fracture healing in vitro and in vivo. Chem Biol Interact. 310(108748)2019.PubMed/NCBI View Article : Google Scholar
16	Kaneko T, Okamura K, Yonemoto Y, Okura C, Suto T, Tachibana M, Sakane H, Inoue M and Chikuda H: Effects of denosumab on bone mineral density and bone turnover markers in rheumatoid arthritis patients switching from bisphosphonates. J Exp Orthop. 6(41)2019.PubMed/NCBI View Article : Google Scholar
17	Cehic M, Lerner RG, Achten J, Griffin XL, Prieto-Alhambra D and Costa ML: Prescribing and adherence to bone protection medications following hip fracture in the United Kingdom: Results from the World Hip Trauma Evaluation (WHiTE) cohort study. Bone Joint J. 101-B:1402–1407. 2019.PubMed/NCBI View Article : Google Scholar
18	Yang F, Yang L, Li Y, Yan G, Feng C, Liu T, Gong R, Yuan Y, Wang N, Idiiatullina E, et al: Melatonin protects bone marrow mesenchymal stem cells against iron overload-induced aberrant differentiation and senescence. J Pineal Res. 63(e12422)2017.PubMed/NCBI View Article : Google Scholar
19	Lopes D, Martins-Cruz C, Oliveira MB and Mano JF: Bone physiology as inspiration for tissue regenerative therapies. Biomaterials. 185:240–275. 2018.PubMed/NCBI View Article : Google Scholar
20	Muruganandan S, Govindarajan R and Sinal CJ: Bone marrow adipose tissue and skeletal health. Curr Osteoporos Rep. 16:434–442. 2018.PubMed/NCBI View Article : Google Scholar
21	Fakhry M, Hamade E, Badran B, Buchet R and Magne D: Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts. World J Stem Cells. 5:136–148. 2013.PubMed/NCBI View Article : Google Scholar
22	Sun MH, Wang WJ, Li Q, Yuan T and Weng WJ: Autologous oxygen release nano bionic scaffold composite miR-106a induced BMSCs enhances osteoblast conversion and promotes bone repair through regulating BMP-2. Eur Rev Med Pharmacol Sci. 22:7148–7155. 2018.PubMed/NCBI View Article : Google Scholar
23	Luo Y, Zhang Y, Miao G, Zhang Y, Liu Y and Huang Y: Runx1 regulates osteogenic differentiation of BMSCs by inhibiting adipogenesis through Wnt/β-catenin pathway. Arch Oral Biol. 97:176–184. 2019.PubMed/NCBI View Article : Google Scholar
24	Qing Y, Huang M, Cao Y, Du T and Song K: Effects of miRNA-342-3p in modulating Hedgehog signaling pathway of human umbilical cord mesenchymal stem cells by down-regulating Sufu. Oral Dis. 25:1147–1157. 2019.PubMed/NCBI View Article : Google Scholar
25	Yang C, Liu X, Zhao K, Zhu Y, Hu B, Zhou Y, Wang M, Wu Y, Zhang C, Xu J, et al: miRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1α pathway and enhances bone regeneration in critical size defects. Stem Cell Res Ther. 10(65)2019.PubMed/NCBI View Article : Google Scholar
26	Hu N, Feng C, Jiang Y, Miao Q and Liu H: Regulative effect of Mir-205 on osteogenic differentiation of bone mesenchymal stem cells (BMSCs): Possible role of SATB2/Runx2 and ERK/MAPK pathway. Int J Mol Sci. 16:10491–10506. 2015.PubMed/NCBI View Article : Google Scholar
27	Shi J, Folwaczny M, Wichelhaus A and Baumert U: Differences in RUNX2 and P2RX7 gene expression between mono- and coculture of human periodontal ligament cells and human osteoblasts under compressive force application. Orthod Craniofac Res. 22:168–176. 2019.PubMed/NCBI View Article : Google Scholar
28	Yang L, Zeng Z, Kang N, Yang JC, Wei X and Hai Y: Circ-VANGL1 promotes the progression of osteoporosis by absorbing miRNA-217 to regulate RUNX2 expression. Eur Rev Med Pharmacol Sci. 23:949–957. 2019.PubMed/NCBI View Article : Google Scholar
29	Polo-Corrales L, Latorre-Esteves M and Ramirez-Vick JE: Scaffold design for bone regeneration. J Nanosci Nanotechnol. 14:15–56. 2014.PubMed/NCBI View Article : Google Scholar