Circulating microRNAs as potential diagnostic biomarkers for osteoporosis

Mandourah, Abdullah Y; Ranganath, L.; Barraclough, Roger; Vinjamuri, Sobhan; Hof, Robert Van'T; Hamill, Sandra; Czanner, Gabriela; Dera, Ayed A.; Wang, Duolao; Barraclough, Dong L.

doi:10.1038/s41598-018-26525-y

Cited by 82 publications

(80 citation statements)

References 43 publications

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“…More recently, screening serum levels of 139 patients, which included controls, osteopenic (with and without fractures), and osteoporotic (with and without fracture), for the presence of circulating miRNAs, found miR122‐5p and miR‐4516 to be present at significantly different levels between nonosteoporotic control, osteopenic, and osteoporosis patients. Specifically, miR‐122‐5p levels were much lower in osteoporosis patients compared with nonosteoporotic control and osteopenic patients.…”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…Moreover, the levels of miR‐4516 were significantly lower in osteoporotic patients with fracture compared with those without. The authors suggested that their results indicate that the decreasing levels of miR‐122‐5p and miR‐4516 in clinical samples might be associated with the development of osteoporosis …”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…The authors selected six miRNAs (miR-187, miR-193a-3p, miR-214, miR518f, miR-636, and miR-210) for further analysis and found that miR-187 levels were 5.3-fold higher in the nonfracture group, whereas miR-518f levels were 8.6-fold higher in bones from fractures of osteoporotic patients; the other four did not show any statistical differences between the two groups. (31) More recently, screening serum levels of 139 patients, (32) which included controls, osteopenic (with and without fractures), and osteoporotic (with and without fracture), for the presence of circulating miRNAs, found miR122-5p and miR-4516 to be present at significantly different levels between nonosteoporotic control, osteopenic, and osteoporosis patients. Specifically, miR-122-5p levels were much lower in osteoporosis patients compared with nonosteoporotic control and osteopenic patients.…”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…The authors suggested that their results indicate that the decreasing levels of miR-122-5p and miR-4516 in clinical samples might be associated with the development of osteoporosis. (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.…”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…Significantly upregulated in serum (30) Osteoporotic fractures miR-187 Significantly downregulated in bone (31) miR-518f Significantly upregulated in bone Osteoporoticfractures miR-122-5p, miR-4516 Significantly downregulated in serum (32) Osteoporoticfractures miR-23b-3p miR-140-3p, miR-885-5p, miR-17-5p, miR-1227-3p, miR-139-5p and miR-197-3p…”

Section: Mirnas and Fracture Repairmentioning

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%

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

Section: Mirnas and Fracture Repairmentioning

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‐19a‐3p Decreases with Age in Mice and Humans and Inhibits Osteoblast Senescence

et al. 2023

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Aging is a major risk factor for most chronic diseases, including osteoporosis, and is characterized by an accumulation of senescent cells in various tissues. MicroRNAs (miRNAs) are critical regulators of bone aging and cellular senescence. Here, we report that miR-19a-3p decreases with age in bone samples from mice as well as in posterior iliac crest bone biopsies of younger versus older healthy women. miR-19a-3p also decreased in mouse bone marrow stromal cells following induction of senescence using etoposide, H 2 O 2 , or serial passaging. To explore the transcriptomic effects of miR-19a-3p, we performed RNA sequencing of mouse calvarial osteoblasts transfected with control or miR-19a-3p mimics and found that miR-19a-3p overexpression significantly altered the expression of various senescence, senescence-associated secretory phenotype-related, and proliferation genes. Specifically, miR-19a-3p overexpression in nonsenescent osteoblasts significantly suppressed p16 Ink4a and p21 Cip1 gene expression and increased their proliferative capacity. Finally, we established a novel senotherapeutic role for this miRNA by treating miR-19a-3p expressing cells with H 2 O 2 to induce senescence. Interestingly, these cells exhibited lower p16 Ink4a and p21 Cip1 expression, increased proliferation-related gene expression, and reduced SA-β-Gal+ cells. Our results thus establish that miR-19a-3p is a senescence-associated miRNA that decreases with age in mouse and human bones and is a potential senotherapeutic target for age-related bone loss.

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MiR‐210‐3p inhibits osteogenic differentiation and promotes adipogenic differentiation correlated with Wnt signaling in ERα‐deficient rBMSCs

Peng

Zhu

et al. 2019

Journal Cellular Physiology

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MicroRNAs (miRNAs) regulate activities in living organisms through various signaling pathways and play important roles in the development and progression of osteoporosis.The balance between osteogenic and adipogenic differentiation of rBMSCs is closely related to the occurrence of osteoporosis. ERα regulates bone metabolism in various tissues. However, the correlation among ERα, miRNAs, and the differentiation of rBMSCs is still unclear. In this study, we used lentivirus transfection into rBMSCs to construct an ERα-deficient model, analyzed the differences in expressed miRNAs between control and ERα-deficient rBMSCs. The results revealed that the expression of 25 miRNAs were upregulated, 164 miRNAs were downregulated, and some of the regulated miRNAs such as miR-210-3p and miR-214-3p were related to osteogenic or adipogenic differentiation, as well as to particular signaling pathways. Next, we overexpressed miR-210-3p to evaluate its effects on the osteogenic and adipogenic differentiation of rBMSCs, and identified the relationship among miR-210-3p, Wnt signaling pathway, and the differentiation of rBMSCs. The results indicated that ERα-deficient inhibited osteogenic differentiation, promoted adipogenic differentiation, and regulated the expression of some miRNAs. Meanwhile, overexpression of miR-210-3p promoted osteogenic differentiation and inhibited adipogenic differentiation of rBMSCs, processes likely to be related to the Wnt signaling pathway. In conclusion, we identified a group of upregulated and downregulated miRNAs in ERα-deficient rBMSCs that might play a vital role in regulating osteogenic or adipogenic differentiation. One of these, miR-210-3p, inhibited osteogenic differentiation and promoted adipogenic differentiation correlated with the Wnt signaling pathway in ERα-deficient rBMSCs, providing new insight into the regulation of bone metabolism.

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Circulating microRNAs as potential diagnostic biomarkers for osteoporosis

Cited by 82 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‐19a‐3p Decreases with Age in Mice and Humans and Inhibits Osteoblast Senescence

MiR‐210‐3p inhibits osteogenic differentiation and promotes adipogenic differentiation correlated with Wnt signaling in ERα‐deficient rBMSCs

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