Serum miRNAs miR-140-3p and miR-23b-3p as potential biomarkers for osteoporosis and osteoporotic fracture in postmenopausal Mexican-Mestizo women

Ramírez‐Salazar, Eric G.; Carrillo-Patiño, Sergio; Hidalgo‐Bravo, Alberto; Rivera‐Paredez, Berenice; Quiterio, Manuel; Ramírez-Palacios, Paula; Patiño, Nelly; Valdés-Flores, Margarita; Salmerón, Jorge; Velázquez‐Cruz, Rafael

doi:10.1016/j.gene.2018.08.074

Cited by 57 publications

(48 citation statements)

References 43 publications

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“…A final clinical study specifically investigated the serum levels of miRNAs in osteopenic, osteoporotic, and osteoporotic‐associated fractures in postmenopausal Mexican women . Screening the expression of 754 miRNAs, the authors found that seven miRNAs (miR‐23b‐3p miR‐140‐3p, miR‐885‐5p, miR‐17‐5p, miR‐1227‐3p, miR‐139‐5p, and miR‐197‐3p) were significantly upregulated in the osteoporotic group.…”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…(32) A final clinical study specifically investigated the serum levels of miRNAs in osteopenic, osteoporotic, and osteoporotic-associated fractures in postmenopausal Mexican women. (33) Screening the expression of 754 miRNAs, the authors found that seven miRNAs (miR-23b-3p miR-140-3p, miR-885-5p, miR-17-5p, miR-1227-3p, miR-139-5p, and miR-197-3p) were significantly upregulated in the osteoporotic group. Further analyses showed that miR-23b-3p and miR-140-3p were significantly upregulated in osteoporotic, osteopenic, and osteoporotic-associated fracture groups, whereas miR-885-5p levels only significantly increased in the osteopenic group, leading the authors to conclude that miR-23b-3p and miR-140-3p can serve as biomarker candidates for osteoporosis in postmenopausal women.…”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…Further analyses showed that miR-23b-3p and miR-140-3p were significantly upregulated in osteoporotic, osteopenic, and osteoporotic-associated fracture groups, whereas miR-885-5p levels only significantly increased in the osteopenic group, leading the authors to conclude that miR-23b-3p and miR-140-3p can serve as biomarker candidates for osteoporosis in postmenopausal women. (33) Animal studies In addition to these clinical studies, several animal miRNA profiling experiments have been reported. Using a model of periosteal cauterization in rats (which results in an atrophic nonunion), Waki and colleagues used microarrays to identify five miRNAs (miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p, and miR-223-3p) as highly upregulated in nonunion and verified these data by PCR analysis that showed their expression peaked on postfracture (PF) day 14 and declined by day 28.…”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…Significantly upregulated in serum (33) Animal studies Rat atrophic nonunion miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p…”

Section: Mirnas and Fracture Repairmentioning

confidence: 99%

“…Serum from osteoporotic fracture patientsupregulated (33) Osteoblast-derivedpromotes osteoblast differentiation (67) Callus from rat nonunion fracturesdownregulated (35) Callus from mouse transverse fracturesupregulated (36)…”

Section: Mir-140-3pmentioning

confidence: 99%

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The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

Hadjiargyrou

Komatsu

2019

Journal of Bone and Mineral Research

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The repair of a fractured bone is critical to the well‐being of humans. Failure of the repair process to proceed normally can lead to complicated fractures, exemplified by either a delay in union or a complete nonunion. Both of these conditions lead to pain, the possibility of additional surgery, and impairment of life quality. Additionally, work productivity decreases, income is reduced, and treatment costs increase, resulting in financial hardship. Thus, developing effective treatments for these difficult fractures or even accelerating the normal physiological repair process is warranted. Accumulating evidence shows that microRNAs (miRNAs), small noncoding RNAs, can serve as key regulatory molecules of fracture repair. In this review, a brief description of the fracture repair process and miRNA biogenesis is presented, as well as a summary of our current knowledge of the involvement of miRNAs in physiological fracture repair, osteoporotic fractures, and bone defect healing. Further, miRNA polymorphisms associated with fractures, miRNA presence in exosomes, and miRNAs as potential therapeutic orthobiologics are also discussed. This is a timely review as several miRNA‐based therapeutics have recently entered clinical trials for nonskeletal applications and thus it is incumbent upon bone researchers to explore whether miRNAs can become the next class of orthobiologics for the treatment of skeletal fractures.

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Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…Significantly upregulated in serum (33) Animal studies Rat atrophic nonunion miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p…”

Section: Mirnas and Fracture Repairmentioning

confidence: 99%

Section: Mir-140-3pmentioning

confidence: 99%

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The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

Hadjiargyrou

Komatsu

2019

Journal of Bone and Mineral Research

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MicroRNA‐543 promotes ovariectomy‐induced osteoporosis through inhibition of AKT/p38 MAPK signaling pathway by targeting YAF2

Ning

Zhao

et al. 2018

J of Cellular Biochemistry

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The present study aimed to determine the roles of miRNA‐543 in osteoporosis in rats induced by ovariectomy. The osteoporosis rat model was established by ovariectomy induction. MiRNA‐543 expression in osteoblasts was measured by quantitative real‐time polymerase chain reaction. The cell proliferation and apoptosis were measured by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and flow cytometry assays, respectively. Western blot analysis was conducted to examine the expression of YAF‐2 and AKT signaling. TargetScan analysis and dual‐luciferase reporter assay were performed to determine the target gene of miRNA‐543. MiRNA‐543 was significantly upregulated in osteoporosis rat model. Overexpression of miRNA‐543 significantly suppressed cell growth and promoted apoptosis in osteoblasts, whereas downregulation of miRNA‐543 significantly enhanced cell growth and inhibited apoptosis. MiRNA‐543 upregulation significantly inhibited YAF‐2 expression and suppressed the phosphorylation and expression of AKT and p38 mitogen‐activated protein kinases (MAPK) in osteoblasts. Furthermore, YAF‐2 knockdown enhanced the effects of miRNA‐543 on apoptosis in osteoblasts. AKT inhibitor MK2206 and p38 MAPK inhibitor SB203580 also enhanced the effects of miRNA‐543 on apoptosis in osteoblasts. Our findings revealed that inhibition of miRNA‐543 could protect osteoblasts against ovariectomy‐induced osteoporosis through AKT/p38 MAPK signaling pathway by targeting YAF2.

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MicroRNA‐218‐5p relieves postmenopausal osteoporosis through promoting the osteoblast differentiation of bone marrow mesenchymal stem cells

Kou

Zheng

Guo

et al. 2019

J of Cellular Biochemistry

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MicroRNAs (miRs) are short noncoding RNAs that play key regulatory roles in osteoblast differentiation. In this study, the specific regulatory roles of miR‐218‐5p on postmenopausal osteoporosis (PMOP) were investigated. The mouse model of PMOP was established by bilateral ovariectomy, and the injection of miR‐218‐5p mimics significantly relieved PMOP degree. Then, bone marrow mesenchymal stem cells (BMMSCs) isolated from PMOP mice were induced into osteoblasts. When compared with normal BMMSCs, PMOP BMMSCs exhibited significantly lower alkaline phosphatase (ALP) activity and less mineralized nodules, as well as downregulated miR‐218‐5p, Runx2, Osterix, COL1A1, and OCN after induction (P < .05). The transfection of miR‐218‐5p mimics, and inhibitor significantly promoted, inhibited the osteoblast differentiation of PMOP BMMSCs, respectively. In addition, COL1A1 was a target of miR‐218‐5p. The transfection of miR‐218‐5p mimics into PMOP BMMSCs significantly upregulated COL1A1 at 14th and 21st day post‐induction, but not at 7th day. Our findings suggest miR‐218‐5p may relieve PMOP through promoting the osteoblast differentiation of BMMSCs.

show abstract

Serum miRNAs miR-140-3p and miR-23b-3p as potential biomarkers for osteoporosis and osteoporotic fracture in postmenopausal Mexican-Mestizo women

Cited by 57 publications

References 43 publications

The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

MicroRNA‐543 promotes ovariectomy‐induced osteoporosis through inhibition of AKT/p38 MAPK signaling pathway by targeting YAF2

MicroRNA‐218‐5p relieves postmenopausal osteoporosis through promoting the osteoblast differentiation of bone marrow mesenchymal stem cells

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