Circulating miR-122-5p and miR-375 as Potential Biomarkers for Bone Mass Recovery after Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Proof-of-Concept Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Circulating miRNA Analysis
2.3. Statistical Analysis
2.4. Target Gene Predictions
3. Results
3.1. Clinical Characteristics of Study Subjects
3.2. Correlation between miRNAs and Study Covariates
3.3. Higher Preoperative Circulating miR-122-5p and miR-375 Expression Levels Were Associated with Slow Recovery of TH BMD in Patients with PHPT
3.4. Patients with High miR-122-5p Levels Had Less CTx Change after Parathyroidectomy
3.5. Association between Known Predictors of BMD Response and Postoperative BMD Changes in Patients with PHPT
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AR | androgen receptor |
IGF1 | insulin like growth factor 1 |
MAPK1 | mitogen-activated protein kinase 1 |
THBS1 | thrombospondin 1 |
ABCB1 | ATP binding cassette subfamily B member 1 |
IL1B | interleukin 1 beta |
LRP6 | low-density lipoprotein receptor-related protein 6 |
BMP2K | bone morphogenic proteins (BMP)-2-inducible kinase |
CALCR | calcitonin receptor |
CNR1 | cannabinoid receptor 1 |
ITGA1 | integrin subunit alpha 1 |
LRP5 | low-density lipoprotein receptor-related protein 5 |
PTK2B | protein tyrosine kinase 2 beta |
RUNX2 | RUNX family transcription factor 2 |
STAT1 | signal transducer and activator of transcription 1 |
VDR | vitamin D receptor |
ALPL | alkaline phosphatase, biomineralization associated |
PLOD1 | procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 |
IL1A | interleukin 1 alpha |
MTHFR | methylenetetrahydrofolate reductase |
PTHLH | parathyroid hormone like hormone |
SOST | sclerostin |
TNF | tumor necrosis factor |
ADM | adrenomedullin |
CDC73 | cell division cycle 73 |
MEN1 | menin 1 |
NOS3 | nitric oxide synthase 3 |
SDHAF2 | succinate dehydrogenase complex assembly factor 2 |
ANKH | ANKH inorganic pyrophosphate transport regulator |
BMP2 | bone morphogenetic protein 2 |
CD47 | cluster of differentiation 47 molecule |
CTSK | cathepsin K |
ESR1 | estrogen receptor 1 |
ESR2 | estrogen receptor 2 |
ICAM1 | intercellular adhesion molecule 1 |
TGFB1 | transforming growth factor beta 1 |
PTH | parathyroid hormone |
IGF1R | insulin like growth factor 1 receptor |
CA10 | carbonic anhydrase 10 |
COL1A1 | collagen type I alpha 1 chain |
FGFBP1 | fibroblast growth factor binding protein 1 |
IL6 | interleukin 6 |
VKORC1 | vitamin K epoxide reductase complex subunit 1 |
CD44 | cluster of differentiation 44 molecule (Indian blood group) |
SLC26A6 | solute carrier family 26 member 6 |
KIT | KIT proto-oncogene, receptor tyrosine kinase |
DKK1 | dickkopf WNT signaling pathway inhibitor 1 |
SPARC | secreted protein acidic and cysteine rich |
References
- Bours, S.P.G.; van Geel, T.A.C.M.; Geusens, P.P.M.M.; Janssen, M.J.W.; Janzing, H.M.J.; Hoffland, G.A.; Willems, P.C.; van den Bergh, J.P.W. Contributors to secondary osteoporosis and metabolic bone diseases in patients presenting with a clinical fracture. J. Clin. Endocrinol. Metab. 2011, 96, 1360–1367. [Google Scholar] [CrossRef] [PubMed]
- Wilczek, M.L.; Kälvesten, J.; Bergström, I.; Pernow, Y.; Sääf, M.; Freyschuss, B.; Brismar, T.B. Can secondary osteoporosis be identified when screening for osteoporosis with digital x-ray radiogrammetry? Initial results from the stockholm osteoporosis project (stop). Maturitas 2017, 101, 31–36. [Google Scholar] [CrossRef]
- Rubin, M.R.; Bilezikian, J.P.; McMahon, D.J.; Jacobs, T.; Shane, E.; Siris, E.; Udesky, J.; Silverberg, S.J. The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J. Clin. Endocrinol. Metab. 2008, 93, 3462–3470. [Google Scholar] [CrossRef] [PubMed]
- Yeh, M.W.; Zhou, H.; Adams, A.L.; Ituarte, P.H.; Li, N.; Liu, I.L.; Haigh, P.I. The relationship of parathyroidectomy and bisphosphonates with fracture risk in primary hyperparathyroidism: An observational study. Ann. Intern. Med. 2016, 164, 715–723. [Google Scholar] [CrossRef] [PubMed]
- Sharma, J.; Itum, D.S.; Moss, L.; Li, C.; Weber, C. Predictors of bone mineral density improvement in patients undergoing parathyroidectomy for primary hyperparathyroidism. World J. Surg. 2014, 38, 1268–1273. [Google Scholar] [CrossRef]
- Nakaoka, D.; Sugimoto, T.; Kobayashi, T.; Yamaguchi, T.; Kobayashi, A.; Chihara, K. Prediction of bone mass change after parathyroidectomy in patients with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 2000, 85, 1901–1907. [Google Scholar] [CrossRef] [PubMed]
- Nomura, R.; Sugimoto, T.; Tsukamoto, T.; Yamauchi, M.; Sowa, H.; Chen, Q.; Yamaguchi, T.; Kobayashi, A.; Chihara, K. Marked and sustained increase in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism; a six-year longitudinal study with or without parathyroidectomy in a japanese population. Clin. Endocrinol. 2004, 60, 335–342. [Google Scholar] [CrossRef] [PubMed]
- Koumakis, E.; Souberbielle, J.C.; Payet, J.; Sarfati, E.; Borderie, D.; Kahan, A.; Cormier, C. Individual site-specific bone mineral density gain in normocalcemic primary hyperparathyroidism. Osteoporos. Int. 2014, 25, 1963–1968. [Google Scholar] [CrossRef] [PubMed]
- Alonso, S.; Ferrero, E.; Donat, M.; Martínez, G.; Vargas, C.; Hidalgo, M.; Moreno, E. The usefulness of high pre-operative levels of serum type i collagen bone markers for the prediction of changes in bone mineral density after parathyroidectomy. J. Endocrinol. Investig. 2012, 35, 640–644. [Google Scholar]
- Tay, Y.D.; Cusano, N.E.; Rubin, M.R.; Williams, J.; Omeragic, B.; Bilezikian, J.P. Trabecular bone score in obese and nonobese subjects with primary hyperparathyroidism before and after parathyroidectomy. J. Clin. Endocrinol. Metab. 2018, 103, 1512–1521. [Google Scholar] [CrossRef] [Green Version]
- Sims, N.A.; Ng, K.W. Implications of osteoblast-osteoclast interactions in the management of osteoporosis by antiresorptive agents denosumab and odanacatib. Curr. Osteoporos. Rep. 2014, 12, 98–106. [Google Scholar] [CrossRef] [PubMed]
- Niederle, M.B.; Foeger-Samwald, U.; Riss, P.; Selberherr, A.; Scheuba, C.; Pietschmann, P.; Niederle, B.; Kerschan-Schindl, K. Effectiveness of anti-osteoporotic treatment after successful parathyroidectomy for primary hyperparathyroidism: A randomized, double-blind, placebo-controlled trial. Langenbeck’s Arch. Surg. 2019, 404, 681–691. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vestergaard, P.; Mollerup, C.L.; Frøkjaer, V.G.; Christiansen, P.M.; Blichert-Toft, M.; Mosekilde, L. Cohort study of fracture risk before and after surgery of primary hyperparathyroidism. Ugeskr. Laeger 2001, 163, 4875–4878. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deiuliis, J.A. Micrornas as regulators of metabolic disease: Pathophysiologic significance and emerging role as biomarkers and therapeutics. Int. J. Obes. 2016, 40, 88–101. [Google Scholar] [CrossRef] [Green Version]
- Párrizas, M.; Novials, A. Circulating micrornas as biomarkers for metabolic disease. Best Pract. Res. Clin. Endocrinol. Metab. 2016, 30, 591–601. [Google Scholar] [CrossRef]
- Mitchell, P.S.; Parkin, R.K.; Kroh, E.M.; Fritz, B.R.; Wyman, S.K.; Pogosova-Agadjanyan, E.L.; Peterson, A.; Noteboom, J.; O’Briant, K.C.; Allen, A.; et al. Circulating micrornas as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA 2008, 105, 10513–10518. [Google Scholar] [CrossRef] [Green Version]
- Yang, Y.; Yujiao, W.; Fang, W.; Linhui, Y.; Ziqi, G.; Zhichen, W.; Zirui, W.; Shengwang, W. The roles of mirna, lncrna and circrna in the development of osteoporosis. Biol. Res. 2020, 53, 40. [Google Scholar] [CrossRef]
- Ko, N.-Y.; Chen, L.-R.; Chen, K.-H. The role of micro rna and long-non-coding rna in osteoporosis. Int. J. Mol. Sci. 2020, 21, 4886. [Google Scholar] [CrossRef]
- Gao, Y.; Patil, S.; Qian, A. The role of micrornas in bone metabolism and disease. Int. J. Mol. Sci. 2020, 21, 6081. [Google Scholar] [CrossRef]
- Ciuffi, S.; Donati, S.; Marini, F.; Palmini, G.; Luzi, E.; Brandi, M.L. Circulating micrornas as novel biomarkers for osteoporosis and fragility fracture risk: Is there a use in assessment risk? Int. J. Mol. Sci. 2020, 21, 6927. [Google Scholar] [CrossRef]
- Pala, E.; Denkçeken, T. Differentially expressed circulating mirnas in postmenopausal osteoporosis: A meta-analysis. Biosci. Rep. 2019, 39, BSR20190667. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bellavia, D.; De Luca, A.; Carina, V.; Costa, V.; Raimondi, L.; Salamanna, F.; Alessandro, R.; Fini, M.; Giavaresi, G. Deregulated mirnas in bone health: Epigenetic roles in osteoporosis. Bone 2019, 122, 52–75. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Li, S.; Li, L.; Li, M.; Guo, C.; Yao, J.; Mi, S. Exosome and exosomal microrna: Trafficking, sorting, and function. Genom. Proteom. Bioinform. 2015, 13, 17–24. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Seeliger, C.; Karpinski, K.; Haug, A.T.; Vester, H.; Schmitt, A.; Bauer, J.S.; van Griensven, M. Five freely circulating mirnas and bone tissue mirnas are associated with osteoporotic fractures. J. Bone Miner. Res. 2014, 29, 1718–1728. [Google Scholar] [CrossRef] [PubMed]
- Verdelli, C.; Sansoni, V.; Perego, S.; Favero, V.; Vitale, J.; Terrasi, A.; Morotti, A.; Passeri, E.; Lombardi, G.; Corbetta, S. Circulating fractures-related micrornas distinguish primary hyperparathyroidism-related from estrogen withdrawal-related osteoporosis in postmenopausal osteoporotic women: A pilot study. Bone 2020, 137, 115350. [Google Scholar] [CrossRef]
- Silverberg, S.J.; Shane, E.; de la Cruz, L.; Dempster, D.W.; Feldman, F.; Seldin, D.; Jacobs, T.P.; Siris, E.S.; Cafferty, M.; Parisien, M.V.; et al. Skeletal disease in primary hyperparathyroidism. J. Bone Miner. Res. 1989, 4, 283–291. [Google Scholar] [CrossRef] [PubMed]
- Dempster, D.W.; Müller, R.; Zhou, H.; Kohler, T.; Shane, E.; Parisien, M.; Silverberg, S.J.; Bilezikian, J.P. Preserved three-dimensional cancellous bone structure in mild primary hyperparathyroidism. Bone 2007, 41, 19–24. [Google Scholar] [CrossRef] [Green Version]
- Dempster, D.; Parisien, M.; Silverberg, S.; Liang, X.-G.; Schnitzer, M.; Shen, V.; Shane, E.; Kimmel, D.; Recker, R.; Lindsay, R. On the mechanism of cancellous bone preservation in postmenopausal women with mild primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 1999, 84, 1562–1566. [Google Scholar] [CrossRef]
- Gracia-Marco, L.; García-Fontana, B.; Ubago-Guisado, E.; Vlachopoulos, D.; García-Martín, A.; Muñoz-Torres, M. Analysis of bone impairment by 3d dxa hip measures in patients with primary hyperparathyroidism: A pilot study. J. Clin. Endocrinol. Metab. 2020, 105, 175–184. [Google Scholar] [CrossRef]
- Cipriani, C.; Abraham, A.; Silva, B.C.; Cusano, N.E.; Rubin, M.R.; McMahon, D.J.; Zhang, C.; Hans, D.; Silverberg, S.J.; Bilezikian, J.P. Skeletal changes after restoration of the euparathyroid state in patients with hypoparathyroidism and primary hyperparathyroidism. Endocrine 2017, 55, 591–598. [Google Scholar] [CrossRef]
- Baim, S.; Wilson, C.R.; Lewiecki, E.M.; Luckey, M.M.; Downs, R.W.; Lentle, B.C. Precision assessment and radiation safety for dual-energy x-ray absorptiometry: Position paper of the international society for clinical densitometry. J. Clin. Densitom. 2005, 8, 371–378. [Google Scholar] [CrossRef]
- Lewiecki, E.M.; Gordon, C.M.; Baim, S.; Leonard, M.B.; Bishop, N.J.; Bianchi, M.L.; Kalkwarf, H.J.; Langman, C.B.; Plotkin, H.; Rauch, F.; et al. International society for clinical densitometry 2007 adult and pediatric official positions. Bone 2008, 43, 1115–1121. [Google Scholar] [CrossRef] [PubMed]
- Zarecki, P.; Hackl, M.; Grillari, J.; Debono, M.; Eastell, R. Serum micrornas as novel biomarkers for osteoporotic vertebral fractures. Bone 2020, 130, 115105. [Google Scholar] [CrossRef] [PubMed]
- McDonald, J.S.; Milosevic, D.; Reddi, H.V.; Grebe, S.K.; Algeciras-Schimnich, A. Analysis of circulating microrna: Preanalytical and analytical challenges. Clin. Chem. 2011, 57, 833–840. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Silver, N.; Best, S.; Jiang, J.; Thein, S.L. Selection of housekee** genes for gene expression studies in human reticulocytes using real-time pcr. BMC Mol. Biol. 2006, 7, 33. [Google Scholar] [CrossRef] [Green Version]
- Pfaffl, M.W.; Tichopad, A.; Prgomet, C.; Neuvians, T.P. Determination of stable housekee** genes, differentially regulated target genes and sample integrity: Bestkeeper--excel-based tool using pair-wise correlations. Biotechnol. Lett. 2004, 26, 509–515. [Google Scholar] [CrossRef] [PubMed]
- Andersen, C.L.; Jensen, J.L.; Ørntoft, T.F. Normalization of real-time quantitative reverse transcription-pcr data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 2004, 64, 5245–5250. [Google Scholar] [CrossRef] [Green Version]
- Vandesompele, J.; De Preter, K.; Pattyn, F.; Poppe, B.; Van Roy, N.; De Paepe, A.; Speleman, F. Accurate normalization of real-time quantitative rt-pcr data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sticht, C.; De La Torre, C.; Parveen, A.; Gretz, N. Mirwalk: An online resource for prediction of microrna binding sites. PLoS ONE 2018, 13. [Google Scholar] [CrossRef]
- Lumachi, F.; Camozzi, V.; Ermani, M.; DE Lotto, F.; Luisetto, G. Bone mineral density improvement after successful parathyroidectomy in pre- and postmenopausal women with primary hyperparathyroidism: A prospective study. Ann. N. Y. Acad. Sci. 2007, 1117, 357–361. [Google Scholar] [CrossRef]
- Steinl, G.K.; Yeh, R.; Walker, M.D.; McManus, C.; Lee, J.A.; Kuo, J.H. Preoperative imaging predicts change in bone mineral density after parathyroidectomy for primary hyperparathyroidism. Bone 2021, 145, 115871. [Google Scholar] [CrossRef] [PubMed]
- **aoling, G.; Shuaibin, L.; Kailu, L. Microrna-19b-3p promotes cell proliferation and osteogenic differentiation of bmscs by interacting with lncrna h19. BMC Med. Genet. 2020, 21, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Tu, Q.; Bonewald, L.F.; He, X.; Stein, G.; Lian, J.; Chen, J. Effects of mir-335-5p in modulating osteogenic differentiation by specifically downregulating wnt antagonist dkk1. J. Bone Miner. Res. 2011, 26, 1953–1963. [Google Scholar] [CrossRef] [Green Version]
- Li, T.; Li, H.; Wang, Y.; Li, T.; Fan, J.; **ao, K.; Zhao, R.C.; Weng, X. Microrna-23a inhibits osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting lrp5. Int. J. Biochem. Cell Biol. 2016, 72, 55–62. [Google Scholar] [CrossRef]
- Hassan, M.Q.; Gordon, J.A.; Beloti, M.M.; Croce, C.M.; Van Wijnen, A.J.; Stein, J.L.; Stein, G.S.; Lian, J.B. A network connecting runx2, satb2, and the mir-23a∼ 27a∼ 24-2 cluster regulates the osteoblast differentiation program. Proc. Natl. Acad. Sci. USA 2010, 107, 19879–19884. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zeng, Y.; Qu, X.; Li, H.; Huang, S.; Wang, S.; Xu, Q.; Lin, R.; Han, Q.; Li, J.; Zhao, R.C. Microrna-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting bmpr2. FEBS Lett. 2012, 586, 2375–2381. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mizuno, Y.; Yagi, K.; Tokuzawa, Y.; Kanesaki-Yatsuka, Y.; Suda, T.; Katagiri, T.; Fukuda, T.; Maruyama, M.; Okuda, A.; Amemiya, T. Mir-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation. Biochem. Biophys. Res. Commun. 2008, 368, 267–272. [Google Scholar] [CrossRef]
- Fan, Q.; Li, Y.; Sun, Q.; Jia, Y.; He, C.; Sun, T. Mir-532-3p inhibits osteogenic differentiation in mc3t3-e1 cells by downregulating ets1. Biochem. Biophys. Res. Commun. 2020, 525, 498–504. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.; Kim, H.J.; Park, C.K.; Kim, Y.-G.; Lee, H.-J.; Kim, J.-Y.; Kim, H.-H. Microrna-124 regulates osteoclast differentiation. Bone 2013, 56, 383–389. [Google Scholar] [CrossRef]
- Qadir, A.S.; Um, S.; Lee, H.; Baek, K.; Seo, B.M.; Lee, G.; Kim, G.-S.; Woo, K.M.; Ryoo, H.-M.; Baek, J.-H. Mir-124 negatively regulates osteogenic differentiation and in vivo bone formation of mesenchymal stem cells. J. Cell. Biochem. 2015, 116, 730–742. [Google Scholar] [CrossRef]
- Cheng, P.; Chen, C.; He, H.B.; Hu, R.; Zhou, H.D.; **e, H.; Zhu, W.; Dai, R.C.; Wu, X.P.; Liao, E.Y. Mir-148a regulates osteoclastogenesis by targeting v-maf musculoaponeurotic fibrosarcoma oncogene homolog b. J. Bone Miner. Res. 2013, 28, 1180–1190. [Google Scholar] [CrossRef] [PubMed]
- Tian, L.; Zheng, F.; Li, Z.; Wang, H.; Yuan, H.; Zhang, X.; Ma, Z.; Li, X.; Gao, X.; Wang, B. Mir-148a-3p regulates adipocyte and osteoblast differentiation by targeting lysine-specific demethylase 6b. Gene 2017, 627, 32–39. [Google Scholar] [CrossRef]
- Feng, L.; **a, B.; Tian, B.-F.; Lu, G.-B. Mir-152 influences osteoporosis through regulation of osteoblast differentiation by targeting rictor. Pharm. Biol. 2019, 57, 586–594. [Google Scholar] [CrossRef] [Green Version]
- Panach, L.; Mifsut, D.; Tarín, J.J.; Cano, A.; García-Pérez, M. Serum circulating micrornas as biomarkers of osteoporotic fracture. Calcif. Tissue Int. 2015, 97, 495–505. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; He, H.; Wang, L.; Jiang, Y.; Xu, Y. Reduced mir-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting rank. Biochem. Cell. Biol. 2018, 96, 627–635. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mandourah, A.Y.; Ranganath, L.; Barraclough, R.; Vinjamuri, S.; Hof, R.V.; Hamill, S.; Czanner, G.; Dera, A.A.; Wang, D.; Barraclough, D.L. Circulating micrornas as potential diagnostic biomarkers for osteoporosis. Sci. Rep. 2018, 8, 8421. [Google Scholar] [CrossRef] [PubMed]
- Kerschan-Schindl, K.; Hackl, M.; Boschitsch, E.; Föger-Samwald, U.; Nägele, O.; Skalicky, S.; Weigl, M.; Grillari, J.; Pietschmann, P. Diagnostic performance of a panel of mirnas (osteomir) for osteoporosis in a cohort of postmenopausal women. Calcif. Tissue Int. 2021, 108, 725–737. [Google Scholar] [CrossRef]
- Komori, T. Regulation of osteoblast differentiation by runx2. In Osteoimmunology; Springer: Boston, MA, USA, 2009; pp. 43–49. [Google Scholar]
- Du, F.; Wu, H.; Zhou, Z.; Liu, Y.U. Microrna-375 inhibits osteogenic differentiation by targeting runt-related transcription factor 2. Exp. Med. 2015, 10, 207–212. [Google Scholar] [CrossRef] [Green Version]
- Sun, T.; Li, C.T.; **ong, L.; Ning, Z.; Leung, F.; Peng, S.; Lu, W.W. Mir-375-3p negatively regulates osteogenesis by targeting and decreasing the expression levels of lrp5 and β-catenin. PLoS ONE 2017, 12, e0171281. [Google Scholar] [CrossRef]
- Meng, Y.C.; Lin, T.; Jiang, H.; Zhang, Z.; Shu, L.; Yin, J.; Ma, X.; Wang, C.; Gao, R.; Zhou, X.H. Mir-122 exerts inhibitory effects on osteoblast proliferation/differentiation in osteoporosis by activating the pcp4-mediated jnk pathway. Mol. Nucleic Acids 2020, 20, 345–358. [Google Scholar] [CrossRef]
- Liao, W.; Ning, Y.; Xu, H.J.; Zou, W.Z.; Hu, J.; Liu, X.Z.; Yang, Y.; Li, Z.H. Bmsc-derived exosomes carrying microrna-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head. Clin. Sci. 2019, 133, 1955–1975. [Google Scholar] [CrossRef]
- Garnero, P.; Ferreras, M.; Karsdal, M.; Nicamhlaoibh, R.; Risteli, J.; Borel, O.; Qvist, P.; Delmas, P.; Foged, N.; Delaissé, J. The type i collagen fragments ictp and ctx reveal distinct enzymatic pathways of bone collagen degradation. J. Bone Miner. Res. 2003, 18, 859–867. [Google Scholar] [CrossRef]
- Kelch, S.; Balmayor, E.R.; Seeliger, C.; Vester, H.; Kirschke, J.S.; van Griensven, M. Mirnas in bone tissue correlate to bone mineral density and circulating mirnas are gender independent in osteoporotic patients. Sci. Rep. 2017, 7, 15861. [Google Scholar] [CrossRef] [PubMed]
- **n, Y.; Liu, Y.; Liu, D.; Li, J.; Zhang, C.; Wang, Y.; Zheng, S. New function of runx2 in regulating osteoclast differentiation via the akt/nfatc1/ctsk axis. Calcif. Tissue Int. 2020, 106, 553–566. [Google Scholar] [CrossRef] [PubMed]
- Coen, G.; Mazzaferro, S.; De Antoni, E.; Chicca, S.; DiSanza, P.; Onorato, L.; Spurio, A.; Sardella, D.; Trombetta, M.; Manni, M.; et al. Procollagen type 1 c-terminal extension peptide serum levels following parathyroidectomy in hyperparathyroid patients. Am. J. Nephrol. 1994, 14, 106–112. [Google Scholar] [CrossRef]
- Guo, C.Y.; Holland, P.A.; Jackson, B.F.; Hannon, R.A.; Rogers, A.; Harrison, B.J.; Eastell, R. Immediate changes in biochemical markers of bone turnover and circulating interleukin-6 after parathyroidectomy for primary hyperparathyroidism. Eur. J. Endocrinol. 2000, 142, 451–459. [Google Scholar] [CrossRef] [Green Version]
- Yeh, M.W.; Ituarte, P.H.G.; Zhou, H.C.; Nishimoto, S.; Amy Liu, I.-L.; Harari, A.; Haigh, P.I.; Adams, A.L. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J. Clin. Endocrinol. Metab. 2013, 98, 1122–1129. [Google Scholar] [CrossRef] [Green Version]
- Bilezikian, J.P.; Cusano, N.E.; Khan, A.A.; Liu, J.-M.; Marcocci, C.; Bandeira, F. Primary hyperparathyroidism. Nat. Rev. Dis. Primers 2016, 2, 16033. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Variables | Total (n = 12) |
---|---|
% Female (n) | 83.3% (10) |
Age (years) | 55.2 ± 14.9 |
Body mass index, kg/m2 | 24.3 ± 3.5 |
Osteoporosis/Osteopenia/Normal, n (%) | 3 (25%)/4 (33%)/5 (42%) |
Laboratory tests (reference value) | |
P1NP, ng/mL (23–83) | 72.5 (44.6–100.6) |
CTX, ng/mL (<0.573) | 0.665 (0.406–1.125) |
PTH, pg/mL (15–65) | 109.7 (96.9–157.8) |
25(OH)D, ng/mL (>20) | 18.9 ± 5.5 |
Corrected Ca, mg/dL (8.5–10.5) | 11.6 (9.8–12.4) |
Phosphate, mg/dL (2.8–4.5) | 2.9 (2.6–3.1) |
ALP, IU/L (52–133) | 89.8 ± 23.0 |
eGFR, mL/min/1.73 m2 (≥60) | 104 (76–110) |
Urinary Ca, mg/24 h (70–180) | 227 ± 105 |
Change in TH BMD from Baseline (%)—1 Year after Surgery | β Coefficient | p-Value |
---|---|---|
hsa-miR-19b-3p | −1.55 | 0.038 * |
hsa-miR-21-5p | −1.11 | 0.282 |
hsa-miR-23a-3p | −0.69 | 0.447 |
hsa-miR-23a-5p | 0.22 | 0.893 |
hsa-miR-24-2-5p | −0.58 | 0.432 |
hsa-miR-24-3p | −0.85 | 0.274 |
hsa-miR-93-5p | −1.33 | 0.113 |
hsa-miR-100-5p | −1.02 | 0.273 |
hsa-miR-122-5p | −2.12 | 0.002 * |
hsa-miR-124-3p | 1.94 | 0.319 |
hsa-miR-125b-5p | −1.14 | 0.395 |
hsa-miR-148-3p | −1.26 | 0.18 |
hsa-miR-152-3p | −1.37 | 0.227 |
hsa-miR-335-5p | −0.68 | 0.561 |
hsa-miR-375 | −1.61 | 0.034 * |
hsa-miR-532-3p | −0.77 | 0.463 |
Change in TH BMD from Baseline (%) | Model I | Model II | Model III | |||
---|---|---|---|---|---|---|
Variables | β coefficient (95% CI) | p-value | β coefficient (95% CI) | p-value | β coefficient (95% CI) | p-value |
miR-19b-3p | −1.55 (−2.99 to −0.10) | 0.038 | −1.31 (−2.71 to 0.08) | 0.062 | −1.08 (−2.26 to 0.10) | 0.067 |
miR-122-5p | −2.12 (−3.29 to −0.95) | 0.002 | −3.00 (−4.56 to −1.45) | 0.002 | −2.60 (−3.88 to −1.32) | 0.003 |
miR-375 | −1.61 (−3.08 to −0.15) | 0.034 | −1.62 (−2.80 to −0.44) | 0.013 | −1.34 (−2.25 to −0.43) | 0.011 |
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Lee, S.; Hong, N.; Kim, Y.; Park, S.; Kim, K.-J.; Jeong, J.; Jung, H.-I.; Rhee, Y. Circulating miR-122-5p and miR-375 as Potential Biomarkers for Bone Mass Recovery after Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Proof-of-Concept Study. Diagnostics 2021, 11, 1704. https://doi.org/10.3390/diagnostics11091704
Lee S, Hong N, Kim Y, Park S, Kim K-J, Jeong J, Jung H-I, Rhee Y. Circulating miR-122-5p and miR-375 as Potential Biomarkers for Bone Mass Recovery after Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Proof-of-Concept Study. Diagnostics. 2021; 11(9):1704. https://doi.org/10.3390/diagnostics11091704
Chicago/Turabian StyleLee, Seunghyun, Namki Hong, Yongnyun Kim, Sunyoung Park, Kyoung-** Kim, Jongju Jeong, Hyo-Il Jung, and Yumie Rhee. 2021. "Circulating miR-122-5p and miR-375 as Potential Biomarkers for Bone Mass Recovery after Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Proof-of-Concept Study" Diagnostics 11, no. 9: 1704. https://doi.org/10.3390/diagnostics11091704