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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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
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
Birkedal-Hansen H (1993) Role of matrix metalloproteinases in human periodontal diseases. J Periodontol 64:474–484
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
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
Delaisse JM, Engsig MT, Everts V et al (2000) Proteinases in bone resorption: obvious and less obvious roles. Clin Chim Acta 291:223–234
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
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
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
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
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
Hannas AR, Pereira JC, Granjeiro JM et al (2007) The role of matrix metalloproteinases in the oral environment. Acta Odontol Scand 65:1–13
Hidalgo M, Eckhardt SG (2001) Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 93:178–193
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
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
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
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
Jurasz P, Chung AW, Radomski A et al (2002) Nonremodeling properties of matrix metalloproteinases: the platelet connection. Circ Res 90:1041–1043
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
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
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
Nguyen M, Arkell J, Jackson CJ (2001) Human endothelial gelatinases and angiogenesis. Int J Biochem Cell Biol 33:960–970
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
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
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
Okamoto T, de Russo MC (1973) Wound healing following tooth extraction. Histochemical study in rats. Rev Fac Odontol Aracatuba 2:153–169
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
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
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
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
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
Sawicki G, Salas E, Murat J et al (1997) Release of gelatinase A during platelet activation mediates aggregation. Nature 386:616–619
Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516
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
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
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
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
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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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