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CircFam190a: a critical positive regulator of osteoclast differentiation via enhancement of the AKT1/HSP90β complex

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주제분류생화학

초록

The identification of key regulatory factors that control osteoclastogenesis is important. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the complexities of circRNA expression as well as the extent of their regulatory functions during osteoclastogenesis have yet to be revealed. Here, based on circular RNA sequencing data, we identified a circular RNA, circFam190a, as a critical regulator of osteoclast differentiation and function. During osteoclastogenesis, circFam190a is significantly upregulated. In vitro, circFam190a enhanced osteoclast formation and function. In vivo, overexpression of circFam190a induced significant bone loss, while knockdown of circFam190a prevented pathological bone loss in an ovariectomized (OVX) mouse osteoporosis model. Mechanistically, our data suggest that circFam90a enhances the binding of AKT1 and HSP90β, promoting AKT1 stability. Altogether, our findings highlight the critical role of circFam190a as a positive regulator of osteoclastogenesis, and targeting circFam190a might be a promising therapeutic strategy for treating pathological bone loss.

Abstract

The identification of key regulatory factors that control osteoclastogenesis is important. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the complexities of circRNA expression as well as the extent of their regulatory functions during osteoclastogenesis have yet to be revealed. Here, based on circular RNA sequencing data, we identified a circular RNA, circFam190a, as a critical regulator of osteoclast differentiation and function. During osteoclastogenesis, circFam190a is significantly upregulated. In vitro, circFam190a enhanced osteoclast formation and function. In vivo, overexpression of circFam190a induced significant bone loss, while knockdown of circFam190a prevented pathological bone loss in an ovariectomized (OVX) mouse osteoporosis model. Mechanistically, our data suggest that circFam90a enhances the binding of AKT1 and HSP90β, promoting AKT1 stability. Altogether, our findings highlight the critical role of circFam190a as a positive regulator of osteoclastogenesis, and targeting circFam190a might be a promising therapeutic strategy for treating pathological bone loss.

참고문헌 (70)

  1. Boyle, W. J., "Osteoclast differentiation and activation", Nature, 423, pp.337~342 (2003)
  2. Teitelbaum, S. L., "Genetic regulation of osteoclast development and function", Nat. Rev. Genet, 4, pp.638~649 (2003)
  3. Väänänen, H. K., "The cell biology of osteoclast function", J. Cell Sci, 113, pp.377~381 (2000)
  4. Roodman, G. D., "Regulation of osteoclast differentiation", Ann. NY Acad. Sci, 1068, pp.100~109 (2006)
  5. Kikuta, J., "Osteoclast migration, differentiation and function : novel therapeutic targets for rheumatic diseases", Rheumatology, 52, pp.226~234 (2013)
  6. Memczak, S., "Circular RNAs are a large class of animal RNAs with regulatory potency", Nature, 495, pp.333~338 (2013)
  7. Qu, S., "Circular RNA : a new star of noncoding RNAs", Cancer Lett, 365, pp.141~148 (2015)
  8. Ebbesen, K. K., "Insights into circular RNA biology", RNA Biol, 14, pp.1035~1045 (2017)
  9. Zhai, Q., "CircRNA hsa_circ_0008500 acts as a miR-1301-3p sponge to promote osteoblast mineralization by upregulating PADI4", Front. Cell Dev. Biol, 8, pp.602731~ (2020)
  10. Li, X., "Circular RNA CDR1as regulates osteoblastic differentiation of periodontal ligament stem cells via the miR-7", GDF5, Stem Cell Res. Ther, pp.2018, 9[DOI]
  11. Mi, B., "CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p", PIK3R1 axis, 2019, pp.11, 11988~12001
  12. Jaiswal, N., "The role of skeletal muscle Akt in the regulation of muscle mass and glucose homeostasis", Mol. Metab, 28, pp.1~13 (2019)
  13. Kawamura, N., "Akt1 in osteoblasts and osteoclasts controls bone remodeling", PLoS ONE, 2, pp.e1058~ (2007)
  14. Sugatani, T., "Akt1", Akt2 and mammalian target of rapamycin, J. Biol. Chem, pp.2005, 280[DOI]
  15. Lee, S. E., "The phosphatidylinositol 3-kinase, p38, and extracellular signalregulated kinase pathways are involved in osteoclast differentiation", Bone, 30, pp.71~77 (2002)
  16. Moon, J. B., "Akt induces osteoclast differentiation through regulating the GSK3β", NFATc1 signaling cascade, 2012, pp.188, 163~169
  17. Suzuki, E., "Akt activation is required for TGF-β1-induced osteoblast differentiation of MC3T3-E1 pre-osteoblasts", PLoS ONE, 9, pp.e112566~ (2014)
  18. Chen, K., "Sfrp4 repression of the Ror2", Jnk cascade in osteoclasts protects cortical bone from excessive endosteal resorption, 2019, pp.116, 14138~14143
  19. Chen, K., "Boldine ameliorates estrogen deficiency-induced bone loss via inhibiting bone resorption", Front. Pharmacol, 9, pp.1046~ (2018)
  20. Gao, Y., "CIRI : an efficient and unbiased algorithm for de novo circular RNA identification", Genome Biol, 16, pp.4~ (2015)
  21. Langmead, B., "Fast gapped-read alignment with Bowtie 2", Nat. Methods, 9, pp.357~359 (2012)
  22. Qiao, K., "LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p", MARK4, J. Exp. Clin. Cancer Res, pp.2019, 38[DOI]
  23. Faulkner, K. G., "The tale of the T-score : review and perspective", Osteoporos. Int, 16, pp.347~352 (2005)
  24. Bouxsein, M. L., "Guidelines for assessment of bone microstructure in rodents using micro-computed tomography", J. Bone Miner. Res, 25, pp.1468~1486 (2010)
  25. Kiper, P. O. S., "Cortical-bone fragility-insights from sFRP4 deficiency in Pyle’s disease", N. Engl. J. Med, 374, pp.2553~2562 (2016)
  26. Movérare-Skrtic, S., "Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures", Nat. Med, 20, pp.1279~1288 (2014)
  27. Zhang, H., "CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα", ATM-p73 axis in bladder cancer, 2021, pp.20, 70~
  28. Li, Q., "CircACC1 regulates assembly and activation of AMPK complex under metabolic stress", Cell Metab, 30, pp.157~173 (2019)
  29. Chen, T., "The genome sequence archive family : toward explosive data growth and diverse data types", Genomics Proteomics Bioinformatics, 19, pp.578~583 (2021)
  30. CNCB-NGDC Members and Partners, "Database Resources of the National Genomics Data Center, China National Center for Bioinformation in 2022", Nucleic Acids Res, 50, pp.27~38 (2022)
  31. Takahashi, N., "Generation of osteoclasts in vitro, and assay of osteoclast activity", Methods Mol. Med, 135, pp.285~301 (2007)
  32. Miyamoto, T., "Differentiation and function of monocyte", macrophage lineage cells and osteoblasts, 2005, pp.63, 1511~1516
  33. Glažar, P., "circBase : a database for circular RNAs", RNA, 20, pp.1666~1670 (2014)
  34. Zeng, Z., "Circular RNA circMAP3K5 acts as a MicroRNA-22-3p sponge to promote resolution of intimal hyperplasia via TET2-mediated smooth muscle cell differentiation", Circulation, 143, pp.354~371 (2021)
  35. Inada, M., "Animal models for bone and joint disease. Ovariectomized and orchidectomized animals", Clin. Calcium, 21, pp.164~170 (2011)
  36. Jee, W. S., "Overview : animal models of osteopenia and osteoporosis", J. Musculoskelet. Neuronal Interact, 1, pp.193~207 (2001)
  37. Huang, A., "Circular RNA-protein interactions : functions, mechanisms, and identification", Theranostics, 10, pp.3503~3517 (2020)
  38. Kristensen, L. S., "The biogenesis, biology and characterization of circular RNAs", Nat. Rev. Genet, 20, pp.675~691 (2019)
  39. Kim, M. J., "Hexosamine biosynthetic pathway-derived O-GlcNAcylation is critical for RANKL-mediated osteoclast differentiation", Int. J. Mol. Sci, 22, pp.8888~ (2021)
  40. Li, J. H., "starBase v2.0: decoding miRNAceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data", Nucleic Acids Res, 42, pp.D92~D97 (2014)
  41. Sato, S., "Modulation of Akt kinase activity by binding to Hsp90", Proc. Natl Acad. Sci. USA, 97, pp.10832~10837 (2000)
  42. Zhang, R., "Hsp90-Akt phosphorylates ASK1 and inhibits ASK1-mediated apoptosis", Oncogene, 24, pp.3954~3963 (2005)
  43. Yun, B. G., "Hsp90 functions to balance the phosphorylation state of Akt during C2C12 myoblast differentiation", Cell. Signal, 17, pp.1477~1485 (2005)
  44. Redlak, M. J., "Targeting PI3K", Akt, Digest. Dis. Sci, pp.2011, 56[DOI]
  45. Giustiniani, J., "Tubulin acetylation favors Hsp90 recruitment to microtubules and stimulates the signaling function of the Hsp90 clients Akt", PKB and p53, 2009, pp.21, 529~539
  46. Haase, M., "HSP90AB1 : helping the good and the bad", Gene, 575, pp.171~186 (2016)
  47. Parikh, C., "Disruption of PH-kinase domain interactions leads to oncogenic activation of AKT in human cancers", Proc. Natl Acad. Sci. USA, 109, pp.19368~19373 (2012)
  48. Basso, A. D., "Akt forms an intracellular complex with heat shock protein 90(Hsp90)and Cdc37 and is destabilized by inhibitors of Hsp90 function", J. Biol. Chem, 277, pp.39858~39866 (2002)
  49. Yang, Y. S., "Bone-targeting AAV-mediated gene silencing in osteoclasts for osteoporosis therapy", Mol. Ther. Methods Clin. Dev, 17, pp.922~935 (2020)
  50. Yang, Y. S., "Bone-targeting AAV-mediated silencing of Schnurri-3 prevents bone loss in osteoporosis", Nat Commun, 10, pp.2958~ (2019)
  51. Zhou, W. Y., "Circular RNA : metabolism, functions and interactions with proteins", Mol. Cancer, 19, pp.172~ (2020)
  52. Wilusz, J. E., "A 360° view of circular RNAs : from biogenesis to functions", Wiley Interdiscip. Rev. RNA, 9, pp.e1478~ (2018)
  53. Wang, W., "Circ_0008542 in osteoblast exosomes promotes osteoclastinduced bone resorption through m6A methylation", Cell Death Dis, 12, pp.628~ (2021)
  54. Gu, C., "CHEK1 and circCHEK1_246aa evoke chromosomal instability and induce bone lesion formation in multiple myeloma", Mol. Cancer, 20, pp.84~ (2021)
  55. Zheng, Y., "The circular RNA landscape of periodontal ligament stem cells during osteogenesis", J. Periodontol, 88, pp.906~914 (2017)
  56. Lin, J., "Circular RNA atlas in osteoclast differentiation with and without alendronate treatment", J. Orthop. Surg. Res, 15, pp.240~ (2020)
  57. Gao, M., "The roles of circRNA-miRNA-mRNA networks in the development and treatment of osteoporosis", Front. Endocrinol, 13, pp.945310~ (2022)
  58. Jiao, M., "Circular RNA and messenger RNA expression profile and competing endogenous RNA network in subchondral bone in osteonecrosis of the femoral head", DNA Cell Biol, 40, pp.61~69 (2021)
  59. Zeng, Q., "The prevalence of osteoporosis in China, a nationwide, multicenter DXA survey", J. Bone Miner. Res, 34, pp.1789~1797 (2019)
  60. Söreskog, E., "Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older", Bone, 134, pp.115286~ (2020)
  61. Clynes, M. A., "The epidemiology of osteoporosis", Br. Med. Bull, 133, pp.105~117 (2020)
  62. Mafi Golchin, M., "Osteoporosis : a silent disease with complex genetic contribution", J. Genet. Genomics, 43, pp.49~61 (2016)
  63. Rachner, T. D., "Osteoporosis: now and the future", Lancet, 377, pp.1276~1287 (2011)
  64. Compston, J., "Practical guidance for the use of bisphosphonates in osteoporosis", Bone, 136, pp.115330~ (2020)
  65. Khosla, S., "Osteoporosis treatment : recent developments and ongoing challenges", Lancet Diabetes Endocrinol, 5, pp.898~907 (2017)
  66. Roberts, T. C., "Advances in oligonucleotide drug delivery", Nat. Rev. Drug Discov, 19, pp.673~694 (2020)
  67. Crooke, S. T., "Antisense technology : an overview and prospectus", Nat. Rev. Drug Discov, 20, pp.427~453 (2021)
  68. Nakamura, A., "Antisense oligonucleotide-based therapies for the treatment of osteoarthritis : opportunities and roadblocks", Bone, 138, pp.115461~ (2020)
  69. Neckers, L., "Hsp90 inhibitors as novel cancer chemotherapeutic agents", Trends Mol. Med, 8, pp.S55~S61 (2002)
  70. Wada, T., "RANKL-RANK signaling in osteoclastogenesis and bone disease", Trends Mol. Med, 12, pp.17~25 (2006)

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