Emerging roles of ADAMTS metalloproteinases in regenerativemedicine and restorative biology

Emerging roles of ADAMTS metalloproteinases in regenerativemedicine and restorative biology

ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteinases degrade proteoglycans and thereby have the potential to alter tissue architecture and regulate cellular function. Recent studies about the roles of these enzymes have produced new perspectives for the molecular mechanisms behind regenerative biology with clinical potential to generate therapeutic targets to resolve tissue injury. ADAMTS enzymes play an important role in the turnover of extracellular matrix proteins in various tissues and their dysregulation has been implicated in disease-related processes such as inflammation and fibrosis. Increasing evidence indicates that they may be of key significance in the physiological and pathological central nervous system. In this review, we summarize what is currently known about the roles of ADAMTS proteins in tissue repair and regeneration as well as in the pathogenesis of other important biological processes and diseases including arthritis, atherosclerosis, and cancer.

___

  • Apte SS (2004). A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motifs: the ADAMTS family. Int J Biochem Cell Biol 36: 981–985.
  • Bai XH, Wang DW, Kong L, Zhang Y, Luan Y, Kobayashi T, Kronenberg HM, Yu XP, Liu CJ (2009). ADAMTS-7, a direct target of PTHrP, adversely regulates endochondral bone growth by associating with and inactivating GEP growth factor. Mol Cell Biol 29: 4201–4219.
  • Cicanic M, Sykova E, Vargova L (2012). Bral1: “Superglue” for the extracellular matrix in the brain white matter. Int J Biochem Cell Biol 44: 596–599.
  • Daar AS (2013). The future of replacement and restorative therapies: from organ transplantation to regenerative medicine. Transplant Proc 45: 3450–3452.
  • Daley WP, Peters SB, Larsen M (2008). Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci 121: 255– 264.
  • Demircan K, Cömertoğlu I, Akyol S, Yigitoğlu BN, Sarikaya E (2014). A new biological marker candidate in female reproductive system diseases: matrix metalloproteinase with thrombospondin motifs (ADAMTS). J Turk Ger Gynecol Assoc 15: 250–255.
  • Demircan K, Yonezawa T, Takigawa T, Topcu V, Erdogan S, Ucar F, Armutcu F, Yigitoglu MR, Ninomiya Y, Hirohata S (2013). ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in Mouse. Neurosci Lett 544: 25–30.
  • Echtermeyer F, Bertrand J, Drejer R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G et al. (2009). Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nat Med 15: 1072–1076.
  • Fosang AJ, Little CB (2008). Drug insight: aggrecanases as therapeutic targets for osteoarthritis. Nat Clin Pract Rheumatol 4: 420–427.
  • Goss RJ (1992). Regeneration versus repair. In: Cohen IK, Diegelman RF, Lindblad WJ, editors. Wound Healing: Biochemical and Clinical Aspects. Philadelphia, PA, USA: WB Saunders, pp. 20–39.
  • Gottschall PE, Howell MD (2015). ADAMTS expression and function in central nervous system injury and disorders. Matrix Biol 44–46C: 70–76.
  • Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008). Wound repair and regeneration. Nature 453: 314–321.
  • Hamel MG, Ajmo JM, Leonardo CC, Zuo F, Sandy JD, Gottschall PE (2008). Multimodal signaling by the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) promotes neurite extension. Exp Neurol 210: 428–440.
  • Hamel MG, Mayer J, Gottschall PE (2005). Altered production and proteolytic processing of brevican by transforming growth factor β in cultured astrocytes. J Neurochem 93: 1533–1541.
  • Hattori N, Carrino DA, Lauer ME, Vasanji A, Wylie JD, Nelson CM, Apte SS (2011). Pericellular versican regulates the fibroblast– myofibroblast transition: a role for ADAMTS5 protease-mediated proteolysis. J Biol Chem 286: 34298–34310.
  • Hernandez-Gea V, Friedman SL (2011). Pathogenesis of liver fibrosis. Annu Rev Pathol 6: 425–456.
  • Hsu YP, Staton CA, Cross N, Buttle DJ (2012). Anti-angiogenic properties of ADAMTS-4 in vitro. Int J Exp Pathol 93: 70–77.
  • Hubmacher D, Apte SS (2013). The biology of the extracellular matrix: novel insights. Curr Opin Rheumatol 25: 65–70.
  • Kalluri R, Zeisberg M (2006). Fibroblasts in cancer. Nat Rev Cancer 6: 392–401.
  • Krstic D, Rodriguez M, Knuesel I (2012). Regulated proteolytic processing of reelin through interplay of tissue plasminogen activator (tPA), ADAMTS-4, ADAMTS-5, and their modulators. PLoS One 7: e47793.
  • Kumar S, Rao N, Ge R (2012). Emerging Roles of ADAMTSs in angiogenesis and cancer. Cancers 4: 1252–1299.
  • Kuno K, Kanada N, Nakashima E, Fujiki F, Ichimura F, Matsushima K (1997). Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J Biol Chem 272: 556–562.
  • Larkin J, Lohr TA, Elefante L, Shearin J, Matico R, Su JL, Xue Y, Liu F, Genell C, Miller RE et al. (2015). Translational development of an ADAMTS-5 antibody for osteoarthritis disease modification. Osteoarthritis Cartilage 23: 1254–1266.
  • Lee JM, Dedhar S, Kalluri R, Thompson EW (2006). The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 172: 973–981.
  • Lemarchant S, Pruvost M, Hebert M, Guberti M, Hommet Y, Briens A, Maubert E, Gueye Y, Feron F, Petite D (2014). tPA promotes ADAMTS-4-induced CSPG degradation, thereby enhancing neuroplasticity following spinal cord injury. Neurobiol Dis 66: 28–42.
  • Lemarchant S, Pruvost M, Montaner J, Emery E, Vivien D, Kanninen K, Koistinaho J (2013). ADAMTS proteoglycanases in the physiological and pathological central nervous system. J Neuroinflammation 10: 133–141.
  • Majumdar MK, Askew R, Schelling S, Stedman N, Blanchet T, Hopkins B, Morris EA, Glasson SS (2007). Double-knockout of ADAMTS-4 and ADAMTS-5 in mice results in physiologically normal animals and prevents the progression of osteoarthritis. Arthritis Rheum 56: 3670–3674.
  • Malfait AM, Liu RQ, Ijiri K, Komiya S, Tortorella MD (2002). Inhibition of ADAM-TS4 and ADAMTS-5 prevents aggrecan degradation in osteoarthritic cartilage. J Biol Chem 277: 22201–22208.
  • Mern DS, Fontana J, Beierfuss A, Thome C, Hegewald AA (2013). A combinatorial relative mass value evaluation of endogenous bioactive proteins in three-dimensional cultured nucleus pulposus cells of herniated intervertebral discs: identification of potential target proteins for gene therapeutic approaches. PLoS One 8: e81467.
  • Mimeault M, Hauke R, Batra SK (2007). Stem cells: a revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies. Clin Pharmacol Ther 82: 252–264.
  • Morawski M, Brückner G, Arendt T, Matthews RT (2012). Aggrecan: beyond cartilage and into the brain. Int J Biochem Cell Biol 44: 690–693.
  • Murphy G, Nagase H (2008). Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat Clin Pract Rheumatol 4: 128–135.
  • Page-McCaw A, Ewald AJ, Werb Z (2007). Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8: 221–233.
  • Pockert AJ, Richardson SM, Le Maitre CL, Lyon M, Deakin JA, Buttle DJ, Freemont AJ, Hoyland JA (2009). Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration. Arthritis Rheum 60: 482–491.
  • Porter S, Clark IM, Kevorkian L, Edward DR (2005) The ADAMTS metalloproteinases. Biochem J 386: 15–27.
  • Reiss K, Saftig P (2009). The “a disintegrin and metalloprotease” (ADAM) family of sheddases: physiological and cellular functions. Semin Cell Dev Biol 20: 126–137.
  • Rodríguez-Manzaneque JC, Fernández-Rodríguez R, Rodríguez-Baena FJ, Iruela-Arispe ML (2015). ADAMTS proteases in vascular biology. Matrix Biol 44–46C: 38–45.
  • Rolls A, Shechter R, Schwartz M (2009). The bright side of the glial scar in CNS repair. Nat Rev Neurosci 10: 235–241.
  • Shiomi T, Lemaitre V, D’Armiento J, Okada Y (2010). Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases. Pathol Int 60: 477–496.
  • Stankunas K, Hang CT, Tsun ZY, Chen H, Lee NV, Wu JI, Shang C, Bayle JH, Shou W, Iruela-Arispe ML et al. (2008). Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis. Dev Cell 14: 298–311.
  • Stanton H, Melrose J, Little CB, Fosang AJ (2011). Proteoglycan degradation by the ADAMTS family of proteinases. Biochim Biophys Acta 1812: 1616–1629.
  • Stupka N, Kintakas C, White JD, Fraser FW, Hanciu M, Aramaki-Hattori N, Martin S, Coles C, Collier F, Ward AC et al. (2013). Versican processing by a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats proteinases-5 and -15 facilitates myoblast fusion. J Biol Chem 288: 1907–1917.
  • Tauchi R, Imagama S, Natori T, Ohgomori T, Muramoto A, Shinjo R, Matsuyama Y, Ishiguro N, Kadomatsu K (2012). The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury. J Neuroinflammation 9: 53–63.
  • Vo NV, Hartman RA, Yurube T, Jacobs LJ, Sowa GA, Kang JD (2013). Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine J 13: 331–341.
  • Wagsater D, Bjork H, Zhu C, Bjorkegren J, Valen G, Hamsten A, Eriksson P (2008). ADAMTS-4 and -8 are inflammatory regulated enzymes expressed in macrophage-rich areas of human atherosclerotic plaques. Atherosclerosis 196: 514–522.
  • Wei A, Shen B, Williams L, Ashish D (2014). Mesenchymal stem cells: potential application in intervertebral disc regeneration. Transl Pediatr 3: 71–90.
  • Werner S, Grose R (2003). Regulation of wound healing by growth factors and cytokines. Physiol Rev 83: 835–870.
  • Wylie JD, Ho JC, Singh S, McCulloch DR, Apte SS (2012). Adamts5 (aggrecanase-2) is widely expressed in the mouse musculoskeletal system and is induced in specific regions of knee joint explants by inflammatory cytokines. J Orthop Res 30: 226–233.
  • Zimmermann DR, Dours-Zimmermann MT (2008). Extracellular matrix of the central nervous system: from neglect to challenge. Histochem Cell Biol 130: 635–653