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Expression of matrix metalloproteinases-2 and -9 and RECK during alveolar bone regeneration in rat

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Abstract

MMPs are endopeptidases that play a pivotal role in ECM turnover. RECK is a single membrane-anchored MMP-regulator. Here, we evaluated the temporal and spatial expression of MMP-2, MMP-9, and RECK during alveolar bone regeneration. The maxillary central incisor of Wistar rats was extracted and the animals were killed at 1, 3, 7, 10, 14, 21, 28, and 42 days post-operatively (n = 3/period). The hemimaxillae were collected, demineralized and embedded in paraffin. Immunohistochemical analysis was performed by the immunoperoxidase technique with polyclonal antibodies. On day 1, polymorphonuclear cells in the blood clot presented mild immunolabeling for MMPs. During bone remodeling, osteoblasts facing new bone showed positive staining for gelatinases and RECK in all experimental periods. MMPs were also found in the connective tissue and endothelial cells. Our results show for the first time that inactive and/or active forms of MMP-2, MMP-9 and RECK are differentially expressed by osteogenic and connective cells during several events of alveolar bone regeneration. This may be important for the replacement of the blood clot by connective tissue, and in the formation, maturation and remodeling of new bone.

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References

  • Apajalahti S, Sorsa T, Railavo S et al (2003) The in vivo levels of matrix metalloproteinase-1 and -8 in gingival crevicular fluid during initial orthodontic tooth movement. J Dent Res 82:1018–1022

    PubMed  CAS  Google Scholar 

  • Battegay EJ, Raines EW, Seifert RA et al (1990) TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell 63:515–524

    Article  PubMed  CAS  Google Scholar 

  • Birkedal-Hansen H (1993) Role of matrix metalloproteinases in human periodontal diseases. J Periodontol 64:474–484

    PubMed  CAS  Google Scholar 

  • Cantarella G, Cantarella R, Caltabiano M et al (2006) Levels of matrix metalloproteinases 1 and 2 in human gingival crevicular fluid during initial tooth movement. Am J Orthod Dentofacial Orthop 130:568.e11–568.e16

    Article  Google Scholar 

  • Clark JC, Thomas DM, Choong PF et al (2007) RECK-a newly discovered inhibitor of metastasis with prognostic significance in multiple forms of cancer. Cancer Metastasis Rev

  • Curran S, Murray GI (2000) Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 36:1621–1630

    Article  PubMed  CAS  Google Scholar 

  • Delaisse JM, Engsig MT, Everts V et al (2000) Proteinases in bone resorption: obvious and less obvious roles. Clin Chim Acta 291:223–234

    Article  PubMed  CAS  Google Scholar 

  • Dew G, Murphy G, Stanton H et al (2000) Localisation of matrix metalloproteinases and TIMP-2 in resorbing mouse bone. Cell Tissue Res 299:385–394

    Article  PubMed  CAS  Google Scholar 

  • Domon S, Shimokawa H, Matsumoto Y et al (1999) In situ hybridization for matrix metalloproteinase-1 and cathepsin K in rat root-resorbing tissue induced by tooth movement. Arch Oral Biol 44:907–915

    Article  PubMed  CAS  Google Scholar 

  • Echizenya M, Kondo S, Takahashi R et al (2005) The membrane-anchored MMP-regulator RECK is a target of myogenic regulatory factors. Oncogene 24:5850–5857

    Article  PubMed  CAS  Google Scholar 

  • Eeckhout Y, Vaes G (1977) Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. Biochem J 166:21–31

    PubMed  CAS  Google Scholar 

  • Everts V, Delaisse JM, Korper W et al (1992) Degradation of collagen in the bone-resorbing compartment underlying the osteoclast involves both cysteine-proteinases and matrix metalloproteinases. J Cell Physiol 150:221–231

    Article  PubMed  CAS  Google Scholar 

  • Hannas AR, Pereira JC, Granjeiro JM et al (2007) The role of matrix metalloproteinases in the oral environment. Acta Odontol Scand 65:1–13

    Article  PubMed  CAS  Google Scholar 

  • Hidalgo M, Eckhardt SG (2001) Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 93:178–193

    Article  PubMed  CAS  Google Scholar 

  • Huebsch RF, Coleman RD, Frandsen AM et al (1952) The healing process following molar extraction. I. Normal male rats (long-evans strain). Oral Surg Oral Med Oral Pathol 5:864–876

    Article  PubMed  CAS  Google Scholar 

  • Igarashi A, Okochi H, Bradham DM et al (1993) Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair. Mol Biol Cell 4:637–645

    PubMed  CAS  Google Scholar 

  • Ignotz RA, Massague J (1986) Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 261:4337–4345

    PubMed  CAS  Google Scholar 

  • Ingman T, Apajalahti S, Mantyla P et al (2005) Matrix metalloproteinase-1 and -8 in gingival crevicular fluid during orthodontic tooth movement: a pilot study during 1 month of follow-up after fixed appliance activation. Eur J Orthod 27:202–207

    Article  PubMed  Google Scholar 

  • Jurasz P, Chung AW, Radomski A et al (2002) Nonremodeling properties of matrix metalloproteinases: the platelet connection. Circ Res 90:1041–1043

    Article  PubMed  CAS  Google Scholar 

  • Monteagudo C, Merino MJ, San-Juan J et al (1990) Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol 136:585–592

    PubMed  CAS  Google Scholar 

  • Mosig RA, Dowling O, DiFeo A et al (2007) Loss of MMP-2 disrupts skeletal and craniofacial development and results in decreased bone mineralization, joint erosion and defects in osteoblast and osteoclast growth. Hum Mol Genet 16:1113–1123

    Article  PubMed  CAS  Google Scholar 

  • Murphy G, Reynolds JJ (1993) Extracellular matrix degradation. In: Royce PM, Steinmann B (eds) Connective tissue and its heritable disorders. Wiley-Liss, New York, pp 287–316

    Google Scholar 

  • Nguyen M, Arkell J, Jackson CJ (2001) Human endothelial gelatinases and angiogenesis. Int J Biochem Cell Biol 33:960–970

    Article  PubMed  CAS  Google Scholar 

  • Noda M, Oh J, Takahashi R et al (2003) RECK: a novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. Cancer Metastasis Rev 22:167–175

    Article  PubMed  CAS  Google Scholar 

  • Nuttall RK, Sampieri CL, Pennington CJ et al (2004) Expression analysis of the entire MMP and TIMP gene families during mouse tissue development. FEBS Lett 563:129–134

    Article  PubMed  CAS  Google Scholar 

  • Oh J, Takahashi R, Kondo S et al (2001) The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 107:789–800

    Article  PubMed  CAS  Google Scholar 

  • Okamoto T, de Russo MC (1973) Wound healing following tooth extraction. Histochemical study in rats. Rev Fac Odontol Aracatuba 2:153–169

    PubMed  CAS  Google Scholar 

  • Okamoto T, Okamoto R, ves Rezende MC et al (1994) Interference of the blood clot on granulation tissue formation after tooth extraction. Histomorphological study in rats. Braz Dent J 5:85–92

    PubMed  CAS  Google Scholar 

  • Redlich M, Reichenberg E, Harari D et al (2001) The effect of mechanical force on mRNA levels of collagenase, collagen type I, and tissue inhibitors of metalloproteinases in gingivae of dogs. J Dent Res 80:2080–2084

    Article  PubMed  CAS  Google Scholar 

  • Rice DP, Kim HJ, Thesleff I (1997) Detection of gelatinase B expression reveals osteoclastic bone resorption as a feature of early calvarial bone development. Bone 21:479–486

    Article  PubMed  CAS  Google Scholar 

  • Sasahara RM, Takahashi C, Noda M (1999a) Involvement of the Sp1 site in ras-mediated downregulation of the RECK metastasis suppressor gene. Biochem Biophys Res Commun 264:668–675

    Article  PubMed  CAS  Google Scholar 

  • Sasahara RM, Takahashi C, Sogayar MC et al (1999b) Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene. Braz J Med Biol Res 32:891–895

    Article  PubMed  CAS  Google Scholar 

  • Sawicki G, Salas E, Murat J et al (1997) Release of gelatinase A during platelet activation mediates aggregation. Nature 386:616–619

    Article  PubMed  CAS  Google Scholar 

  • Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516

    Article  PubMed  CAS  Google Scholar 

  • Takahashi C, Sheng Z, Horan TP et al (1998) Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proc Natl Acad Sci USA 95:13221–13226

    Article  PubMed  CAS  Google Scholar 

  • Takahashi I, Onodera K, Nishimura M et al (2006) Expression of genes for gelatinases and tissue inhibitors of metalloproteinases in periodontal tissues during orthodontic tooth movement. J Mol Histol 37:333–342

    Article  PubMed  CAS  Google Scholar 

  • Tennenbaum R, Shklar G (1970) The effect of an anabolic steroid on the healing of experimental extraction wounds. Oral Surg Oral Med Oral Pathol 30:824–834

    Article  PubMed  CAS  Google Scholar 

  • Trowbridg HO, Emmlig RC (1996) A review of the process. 4:137–151

  • Wahl SM, Allen JB, Welch GR et al (1992) Transforming growth factor-beta in synovial fluids modulates Fc gamma RII (CD16) expression on mononuclear phagocytes. J Immunol 148:485–490

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the participation of MS Luciana C. S. Oliveira and the Financial support provided by Fapesp (fellowship to Willian Fernando Zambuzzi 02/03928-0, Grant 99/10655-5, and Thematic Project grant 01/10707), CAPES (fellowship to Katiucia Batista da Silva Paiva), and CNPq Grant. n. 475721/2003-9.

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Correspondence to José Mauro Granjeiro.

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Accorsi-Mendonça, T., Paiva, K.B.d.S., Zambuzzi, W.F. et al. Expression of matrix metalloproteinases-2 and -9 and RECK during alveolar bone regeneration in rat. J Mol Hist 39, 201–208 (2008). https://doi.org/10.1007/s10735-007-9152-z

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  • DOI: https://doi.org/10.1007/s10735-007-9152-z

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