Circulating microRNAs as potential diagnostic biomarkers for osteoporosis

被引:87
作者
Mandourah, Abdullah Y. [1 ,8 ]
Ranganath, Lakshminarayan [2 ]
Barraclough, Roger [3 ]
Vinjamuri, Sobhan [4 ]
Van'T Hof, Robert [1 ]
Hamill, Sandra [4 ]
Czanner, Gabriela [5 ]
Dera, Ayed A. [1 ,7 ]
Wang, Duolao [6 ]
Barraclough, Dong L. [1 ]
机构
[1] Univ Liverpool, Inst Ageing & Chron Dis, Dept Musculoskeletal Biol, William Henry Duncan Bldg,6 West Derby St, Liverpool L7 8TX, Merseyside, England
[2] Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Clin Biochem & Metab Med, Prescot St, Liverpool L7 8XP, Merseyside, England
[3] Univ Liverpool, Inst Integrat Biol, Dept Biochem, Biosci Bldg,Crown St, Liverpool L69 7ZB, Merseyside, England
[4] Royal Liverpool & Broadgreen Univ Hosp NHS Trust, Dept Nucl Med, Prescot St, Liverpool L7 8XP, Merseyside, England
[5] Fac Hlth & Life Sci, Dept Biostat & Eye & Vis Sci, William Henry Duncan Bldg,6 West Derby St, Liverpool L7 8TX, Merseyside, England
[6] Univ Liverpool Liverpool Sch Trop Med, Dept Clin Sci, Pembroke Pl, Liverpool L3 5QA, Merseyside, England
[7] King Khalid Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Abha, Saudi Arabia
[8] Al Hada Armed Forces Hosp, At Taif, Saudi Arabia
关键词
POSTMENOPAUSAL OSTEOPOROSIS; VITAMIN-D; BONE; EXPRESSION; MIRNAS; SERUM; DIFFERENTIATION; OSTEOBLASTS; SIGNATURES; FRACTURES;
D O I
10.1038/s41598-018-26525-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Osteoporosis is the most common age-related bone disease worldwide and is usually clinically asymptomatic until the first fracture happens. MicroRNAs are critical molecular regulators in bone remodelling processes and are stabilised in the blood. The aim of this project was to identify circulatory microRNAs associated with osteoporosis using advanced PCR arrays initially and the identified differentially-expressed microRNAs were validated in clinical samples using RT-qPCR. A total of 161 participants were recruited and 139 participants were included in this study with local ethical approvals prior to recruitment. RNAs were extracted, purified, quantified and analysed from all serum and plasma samples. Differentially-expressed miRNAs were identified using miRNA PCR arrays initially and validated in 139 serum and 134 plasma clinical samples using RT-qPCR. Following validation of identified miRNAs in individual clinical samples using RT-qPCR, circulating miRNAs, hsa-miR-122-5p and hsa-miR-4516 were statistically significantly differentially-expressed between non-osteoporotic controls, osteopaenia and osteoporosis patients. Further analysis showed that the levels of these microRNAs were associated with fragility fracture and correlated with the low bone mineral density in osteoporosis patients. The results show that circulating hsa-miR-122-5p and hsa-miR-4516 could be potential diagnostic biomarkers for osteoporosis in the future.
引用
收藏
页数:10
相关论文
共 46 条
[1]   Predicting effective microRNA target sites in mammalian mRNAs [J].
Agarwal, Vikram ;
Bell, George W. ;
Nam, Jin-Wu ;
Bartel, David P. .
ELIFE, 2015, 4
[2]   Changes of Circulating MicroRNAs in Response to Treatment With Teriparatide or Denosumab in Postmenopausal Osteoporosis [J].
Anastasilakis, Athanasios D. ;
Makras, Polyzois ;
Pikilidou, Maria ;
Tournis, Symeon ;
Makris, Konstantinos ;
Bisbinas, Ilias ;
Tsave, Olga ;
Yovos, John G. ;
Yavropoulou, Maria P. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2018, 103 (03) :1206-1213
[3]   Cannabinoid receptors and the regulation of bone mass [J].
Bab, I. ;
Zimmer, A. .
BRITISH JOURNAL OF PHARMACOLOGY, 2008, 153 (02) :182-188
[4]   MiR-148a the epigenetic regulator of bone homeostasis is increased in plasma of osteoporotic postmenopausal women [J].
Bedene, Ajda ;
Bedrac, Simona Mencej ;
Jese, Lea ;
Marc, Janja ;
Vrtacnik, Peter ;
Prezelj, Janez ;
Kocjan, Tomaz ;
Kranjc, Tilen ;
Ostanek, Barbara .
WIENER KLINISCHE WOCHENSCHRIFT, 2016, 128 :519-526
[5]   ROLE AND REGULATION OF RUNX2 IN OSTEOGENESIS [J].
Bruderer, M. ;
Richards, R. G. ;
Alini, M. ;
Stoddart, M. J. .
EUROPEAN CELLS & MATERIALS, 2014, 28 :269-286
[6]   Large-scale genome-wide screening of circulating microRNAs in clear cell renal cell carcinoma reveals specific signatures in late stage disease [J].
Chanudet, Estelle ;
Wozniak, Magdalena B. ;
Bouaoun, Liacine ;
Byrnes, Graham ;
Mukeriya, Anush ;
Zaridze, David ;
Brennan, Paul ;
Muller, David C. ;
Scelo, Ghislaine .
INTERNATIONAL JOURNAL OF CANCER, 2017, 141 (09) :1730-1740
[7]   hsa-miR-4516 Mediated Downregulation of STAT3/CDK6/UBE2N Plays a Role in PUVA Induced Apoptosis in Keratinocytes [J].
Chowdhari, Shruti ;
Saini, Neeru .
JOURNAL OF CELLULAR PHYSIOLOGY, 2014, 229 (11) :1630-1638
[8]   The new bone biology: Pathologic, molecular, and clinical correlates [J].
Cohen, M. Michael, Jr. .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2006, 140A (23) :2646-2706
[9]   Vitamin D and gene networks in human osteoblasts [J].
de Peppel, Jeroen van ;
van Leeuwen, Johannes P. T. M. .
FRONTIERS IN PHYSIOLOGY, 2014, 5
[10]   miRWalk2.0: a comprehensive atlas of microRNA-target interactions [J].
Dweep, Harsh ;
Gretz, Norbert .
NATURE METHODS, 2015, 12 (08) :697-697