Rol de los micro-ARN osteoblásticos en el esqueleto: desde las funciones biológicas al potencial terapéutico

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Farzin Takyar
Alyssa Bren
Leslie R. Morse
Ricardo A. Battaglino

Resumen

Los micro-ARNs (miARNss) son pequeños ARN no codificantes que desempeñan un papel fundamental en la regulación génica postranscripcional. Ejercen su función al unirse a moléculas de ARN mensajero (ARNm), promoviendo su degradación e inhibiendo su
traducción en proteínas. En el contexto de las enfermedades esqueléticas, como la osteoporosis, la osteoartritis y la metástasis ósea existe evidencia de que los miARNs osteoblásticos están involucrados en la  regulación de la formación y del mantenimiento óseo.
Los osteoblastos son células formadoras de hueso responsables de sintetizar y depositar la matriz extracelular, que finalmente se mineraliza para formar el hueso. Los miARNs derivados de osteoblastos modulan varios aspectos de la función de estas células, incluida la proliferación, diferenciación, mineralización y la apoptosis. La desregulación de estos miARNs puede  alterar el equilibrio entre la formación y la resorción ósea, lo que lleva a enfermedades óseas.
Las implicaciones terapéuticas de los miARNs osteoblásticos en enfermedades esqueléticas son significativas. La modulación de los niveles de expresión de miARNs específicos es prometedora para desarrollar nuevas estrategias terapéuticas a fin de mejorar la formación, prevenir la pérdida y promover la  regeneración ósea. Los enfoques terapéuticos potenciales incluyen el uso de miméticos de miARNs para restaurar la expresión de miARNs o el uso de
oligonucleótidos anti-miARNs para inhibir su función.
Las terapias basadas en miARNs aún se encuentran
en las primeras etapas de desarrollo. La administración de miARNs a las células y los tejidos específicos sigue siendo un desafío para lograr una aplicación clínica eficaz. 

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Takyar F, Bren A, Morse LR, Battaglino RA. Rol de los micro-ARN osteoblásticos en el esqueleto: desde las funciones biológicas al potencial terapéutico. Actual. Osteol. [Internet]. 15 de agosto de 2023 [citado 18 de julio de 2024];19(1):p. 18-29. Disponible en: https://ojs.osteologia.org.ar/ojs33010/index.php/osteologia/article/view/79
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Cech TR, Steitz JA. The noncoding RNA revolution-trashing old rules to forge new ones. Cell 2014; 157(1): 77-94.

Lau NC, et al. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001; 294(5543):858-62.

Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science 2001; 294(5543):862-4.

Hammond SM. An overview of microRNAs. Adv Drug Deliv Rev 2015; 87:3-14.

Fabris L et al. The Potential of MicroRNAs as Prostate Cancer Biomarkers. Eur Urol 2016; 70(2): 312-22.

Hibner G, Kimsa-Furdzik M, Francuz T. Relevance of MicroRNAs as Potential Diagnostic and Prognostic Markers in Colorectal Cancer. Int J Mol Sci 2018; 19(10):2944.

Kalayinia S, et al. MicroRNAs: roles in cardiovascular development and disease. Cardiovasc Pathol 2021; 50: 107296.

Choi YJ et al. Deficiency of DGCR8 increases bone formation through downregulation of miR-22 expression. Bone 2017; 103:287-294.

O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne) 2018; 9:402-410.

Harfe BD, et al. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci USA 2005; 102(31): 10898-903.

Gaur T et al. Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse. Dev Biol 2010; 340):10-21.

Bendre A., et al. Dicer1 ablation in osterix positive bone forming cells affects cortical bone homeostasis. Bone 2018; 106:139-147.

Zhou J. et al. Dicer-dependent pathway contribute to the osteogenesis mediated by regulation of Runx2. Am J Transl Res 2016; 8:5354-5369.

Zuo B et al. microRNA-103a functions as a mechanosensitive microRNA to inhibit bone formation through targeting Runx2. J Bone Miner Res 2015; 30(2):330-45.

Sun Z. et al. MiR-103-3p targets the m(6) A methyltransferase METTL14 to inhibit osteoblastic bone formation. Aging Cell 2021; 20(2): e13298.

Hu Z et al. miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity. Sci Rep 2015; 5: e18655.

Zeng X. et al. Puerarin inhibits TRPM3/miR-204 to promote MC3T3-E1 cells proliferation, differentiation and mineralization. Phytother Res 2018; 32(6): 996-1003.

Kou J. et al. MicroRNA-218-5p relieves postmenopausal osteoporosis through promoting the osteoblast differentiation of bone marrow mesenchymal stem cells. J Cell Biochem 2020; 121(2):1216-1226.

Yang L et al. miR-93/Sp7 function loop mediates osteoblast mineralization. J Bone Miner Res 2012; 27(7):1598-606.

Jia J et al. miR-145 suppresses osteogenic differentiation by targeting Sp7. FEBS Lett 2013; 587(18):3027-31.

Hassan MQ et al. BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network. J Biol Chem 2006; 281(52):40515-26.

Harris SE et al. Transcriptional regulation of BMP-2 activated genes in osteoblasts using gene expression microarray analysis: role of Dlx2 and Dlx5 transcription factors. Front Biosci 2003; 8:s1249-65.

Hassan MQ et al. Dlx3 transcriptional regulation of osteoblast differentiation: temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene. Mol Cell Biol 2004; 24(20):9248-61.

Lee HL et al. Distal-less homeobox 5 inhibits adipogenic differentiation through the down-regulation of peroxisome proliferator-activated receptor gamma expression. J Cell Physiol 2013; 228(1):87-98.

Shirazi S et al. The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation. Sci Rep 2021; 11(1):5953.

Yang X et al. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell 2004; 117(3):387-98.

Wang X et al. miR-214 targets ATF4 to inhibit bone formation. Nat Med 2013.; 19(1):93-100.

Zhao C et al. miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway. RNA Biol 2015; 12(3):343-53.

Li, D., et al., Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun, 2016. 7: p. 10872.

Pi C et al. The expression and function of microRNAs in bone homeostasis. Front Biosci (Landmark Ed) 2015; 20(1):119-38.

Vimalraj S, Slvmurugan N. MicroRNAs: Synthesis, Gene Regulation and Osteoblast Differentiation. Curr Issues Mol Biol 2013; 15:7-18.

Liu J et al. microRNA-Mediated Regulation of Bone Remodeling: A Brief Review. JBMR Plus 2019; 3(9):e10213.

Tang X et al. MicroRNA-433-3p promotes osteoblast differentiation through targeting DKK1 expression. PLoS One 2017; 12(6):e0179860.

Ponzetti M, Rucci N. Osteoblast Differentiation and Signaling: Established Concepts and Emerging Topics. Int J Mol Sci 2021. 22(13): 6651.

Mohanapriya R, Akshaya RL, Selvamurugan N. A regulatory role of circRNA-miRNA-mRNA network in osteoblast differentiation. Biochimie 2022; 193:137-147.

Narayanan A et al. Regulation of Runx2 by MicroRNAs in osteoblast differentiation. Life Sci 2019; 232:116676.

Baglio SR et al. MicroRNA expression profiling of human bone marrow mesenchymal stem cells during osteogenic differentiation reveals Osterix regulation by miR-31. Gene 2013; 527(1):321-31.

Zhang JF et al. MiR-637 maintains the balance between adipocytes and osteoblasts by directly targeting Osterix. Mol Biol Cell 2011; 22(21):3955-61.

Rodan GA, Martin TJ. Role of osteoblasts in hormonal control of bone resorption-a hypothesis. Calcif Tissue Int. 1981; 33(4):349-51.

Walsh MC, Choi Y. Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond. Front Immunol. 2014; 5:511-18.

Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003; 423(6937):337-42.

Ji L, Li X, He S, Chen S. Regulation of osteoclast-mediated bone resorption by microRNA. Cell Mol Life Sci 2022; 79(6):287-292.

Chen C et al. MiR-503 regulates osteoclastogenesis via targeting RANK. J Bone Miner Res 2014; 29(2):338-47.

Huang MZ et al. Artesunate inhibits osteoclastogenesis through the miR-503/RANK axis. Biosci Rep 2020; 40(7):BSR20194387.

Wang C et al. Reduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK. Biochem Cell Biol 2018; 96(5):627-635.

Wang W et al. Circ_0008542 in osteoblast exosomes promotes osteoclast-induced bone resorption through m6A methylation. Cell Death Dis 2021; 12(7):628-34.

Li M et al. MicroRNA-21 affects mechanical force-induced midpalatal suture remodelling. Cell Prolif, 2020; 53(1):e12697.

Pitari MR et al. Inhibition of miR-21 restores RANKL/OPG ratio in multiple myeloma-derived bone marrow stromal cells and impairs the resorbing activity of mature osteoclasts. Oncotarget 2015; 6(29):27343-58.

Suarjana IN et al. The Role of Serum Expression Levels of Microrna-21 on Bone Mineral Density in Hypostrogenic Postmenopausal Women with Osteoporosis: Study on Level of RANKL, OPG, TGFbeta-1, Sclerostin, RANKL/OPG Ratio, and Physical Activity. Acta Med Indones 2019; 51(3): 245-252.

Wang S et al. miR‑21 promotes osteoclastogenesis through activation of PI3K/Akt signaling by targeting Pten in RAW264.7 cells. Mol Med Rep 2020; 21(3):1125-1132.

Gong N et al. Keratinocytes-derived exosomal miRNA regulates osteoclast differentiation in middle ear cholesteatoma. Biochem Biophys Res Commun, 2020; 525(2):341-347.

Chen Y et al. miR-145-5p Increases Osteoclast Numbers In Vitro and Aggravates Bone Erosion in Collagen-Induced Arthritis by Targeting Osteoprotegerin. Med Sci Monit 2018; 24:5292-5300.

Chen H et al. MYC-mediated miR-320a affects receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast formation by regulating phosphatase and tensin homolog (PTEN). Bioengineered 2021; 12(2):12677-12687.

Sun L, Lian JX, Meng S. MiR-125a-5p promotes osteoclastogenesis by targeting TNFRSF1B. Cell Mol Biol Lett 2019; 24:e23.

Zhao C et al. miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway. RNA Biol 2015; 12(3):343-53.

Gong M et al. miR-335 inhibits small cell lung cancer bone metastases via IGF-IR and RANKL pathways. Mol Cancer Res 2014; 12(1):101-10.

Wang T et al. MicroRNA-106b inhibits osteoclastogenesis and osteolysis by targeting RANKL in giant cell tumor of bone. Oncotarget 2015; 6(22):18980-96.

Tao Y et al. Downregulation of miR-106b attenuates inflammatory responses and joint damage in collagen-induced arthritis. Rheumatology (Oxford) 2017; 56(10):1804-1813.

Li W et al. MiR-377 inhibits wear particle-induced osteolysis via targeting RANKL. Cell Biol Int 2019; 43(6):658-668.

Han Z et al. miR-181b/Oncostatin m axis inhibits prostate cancer bone metastasis via modulating osteoclast differentiation. J Cell Biochem 2020; 121(2):1664-1674.

Li G et al.The protective effects of microRNA-26a in steroid-induced osteonecrosis of the femoral head by repressing EZH2. Cell Cycle 2020; 19(5):551-566.

Kim K et al. MicroRNA-26a regulates RANKL-induced osteoclast formation. Mol Cells 2015; 38(1): 75-80.

Wang Q et al. Osteoblasts-derived exosomes regulate osteoclast differentiation through miR-503-3p/Hpse axis. Acta Histochem 2021; 123(7):151790.

Guo S. et al. GATA4-driven miR-206-3p signatures control orofacial bone development by regulating osteogenic and osteoclastic activity. Theranostics 2021; 11(17):8379-8395.

Li J et al. miR-101-3p/Rap1b signal pathway plays a key role in osteoclast differentiation after treatment with bisphosphonates. BMB Rep 2019; 52(9):572-576.

Zhou L et al. MicroRNA‑100‑5p inhibits osteoclastogenesis and bone resorption by regulating fibroblast growth factor 21. Int J Mol Med 2019; 43(2):727-738.

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