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Erschienen in: Clinical Oral Investigations 7/2016

06.11.2015 | Original Article

Accelerated degradation of collagen membranes in diabetic rats is associated with increased infiltration of macrophages and blood vessels

verfasst von: Ofer Moses, Meizi Eliezer, Carlos Nemcovsky, Haim Tal, Miron Weinreb

Erschienen in: Clinical Oral Investigations | Ausgabe 7/2016

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Abstract

Objectives

Increased collagenolytic activity in diabetes may compromise collagen membrane (CM) survival. Tetracycline (TTC) possesses anti-collagenolytic properties and delays CM degradation. This study evaluated macrophage and capillary infiltration within CMs in diabetic rats.

Materials and methods

Diabetes was induced in 20 Wistar rats by streptozotocin and 20 served as controls. Biotin-labeled CM discs were immersed in either TTC (50 mg/ml) or PBS. In each animal, 2 discs (TTC and control) were implanted under the parietal periosteum and rats were sacrificed at 2 or 4 weeks post-implantation. The area and thickness of the residual disc collagen were measured following staining with streptavidin, and the number of macrophages and blood vessels within the membranes was determined using specific antibodies (to CD68 and transglutaminase II, respectively).

Results

Diabetes significantly reduced the area and thickness of the CMs, while TTC increased CM thickness significantly in both groups of rats at 2 and 4 weeks. Diabetes increased the number of macrophages (∼eightfold at 2 weeks and ∼fourfold at 4 weeks), but TTC had no significant effect. Finally, diabetes increased the number of blood vessels within the discs (∼threefold at 2 weeks and ∼twofold at 4 weeks), while TTC had no effect.

Conclusions

Diabetes increases degradation of native CMs and the number of blood vessels and macrophages within them. TTC immersion delays CM degradation without an apparent effect on macrophage and blood vessel penetration.

Clinical relevance

Enhanced CM degradation in diabetic conditions which impair guided regenerative procedure outcome is apparently related to increased blood vessel formation and macrophage infiltration.
Literatur
1.
Zurück zum Zitat Lundgren D, Laurell L, Gottlow J, Rylander H, Mathisen T, Nyman S, Rask M (1995) The influence of the design of two different bioresorbable barriers on the results of guided tissue regeneration therapy. An intra-individual comparative study in the monkey. J Periodontol 66:605–612CrossRefPubMed Lundgren D, Laurell L, Gottlow J, Rylander H, Mathisen T, Nyman S, Rask M (1995) The influence of the design of two different bioresorbable barriers on the results of guided tissue regeneration therapy. An intra-individual comparative study in the monkey. J Periodontol 66:605–612CrossRefPubMed
2.
Zurück zum Zitat Patino MG, Neiders ME, Andreana S, Noble B, Cohen RE (2002) Collagen as an implantable material in medicine and dentistry. J Oral Implantol 28:220–225CrossRefPubMed Patino MG, Neiders ME, Andreana S, Noble B, Cohen RE (2002) Collagen as an implantable material in medicine and dentistry. J Oral Implantol 28:220–225CrossRefPubMed
3.
Zurück zum Zitat Pfeifer J, Van Swol RL, Ellinger R (1989) Epithelial exclusion and tissue regeneration using a collagen membrane barrier in chronic periodontal defects: a histologic study. Int J Periodontics Restorative Dent 9:262–273PubMed Pfeifer J, Van Swol RL, Ellinger R (1989) Epithelial exclusion and tissue regeneration using a collagen membrane barrier in chronic periodontal defects: a histologic study. Int J Periodontics Restorative Dent 9:262–273PubMed
4.
Zurück zum Zitat Tal H, Kozlovsky A, Artzi Z, Nemcovsky CE, Moses O (2008) Cross-linked and non-cross-linked collagen barrier membranes disintegrate following surgical exposure to the oral environment: a histological study in the cat. Clin Oral Implants Res 19:760–766CrossRefPubMed Tal H, Kozlovsky A, Artzi Z, Nemcovsky CE, Moses O (2008) Cross-linked and non-cross-linked collagen barrier membranes disintegrate following surgical exposure to the oral environment: a histological study in the cat. Clin Oral Implants Res 19:760–766CrossRefPubMed
5.
Zurück zum Zitat Chung KM, Salking LM, Stein MD, Freedman AL (1990) Clinical evaluation of biodegradable collagen membrane in GTR. J Periodontol 61:732–736CrossRefPubMed Chung KM, Salking LM, Stein MD, Freedman AL (1990) Clinical evaluation of biodegradable collagen membrane in GTR. J Periodontol 61:732–736CrossRefPubMed
6.
Zurück zum Zitat Zitzmann NU, Naef R, Schärer P (1997) Resorbable versus nonresorbable membranes in combination with Bio-Oss for guided bone regeneration. Int J Oral Maxillofac Implants 12:844–852PubMed Zitzmann NU, Naef R, Schärer P (1997) Resorbable versus nonresorbable membranes in combination with Bio-Oss for guided bone regeneration. Int J Oral Maxillofac Implants 12:844–852PubMed
7.
Zurück zum Zitat Machtei EE (2001) The effect of membrane exposure on the outcome of regenerative procedures in humans: a meta-analysis. J Periodontol 72:512–516CrossRefPubMed Machtei EE (2001) The effect of membrane exposure on the outcome of regenerative procedures in humans: a meta-analysis. J Periodontol 72:512–516CrossRefPubMed
8.
Zurück zum Zitat Tal H, Kozlovsky A, Artzi Z, Nemcovsky CE, Moses O (2008) Long-term bio-degradation of cross-linked and non-cross-linked collagen barriers in human guided bone regeneration. Clin Oral Implants Res 19:295–230CrossRefPubMed Tal H, Kozlovsky A, Artzi Z, Nemcovsky CE, Moses O (2008) Long-term bio-degradation of cross-linked and non-cross-linked collagen barriers in human guided bone regeneration. Clin Oral Implants Res 19:295–230CrossRefPubMed
9.
Zurück zum Zitat Reynolds JJ, Hembry RM, Meikle MC (1994) Connective tissue degradation in health and periodontal disease and the roles of matrix metalloproteinases and their natural inhibitors. Adv Dent Res 8:312–319PubMed Reynolds JJ, Hembry RM, Meikle MC (1994) Connective tissue degradation in health and periodontal disease and the roles of matrix metalloproteinases and their natural inhibitors. Adv Dent Res 8:312–319PubMed
10.
Zurück zum Zitat Armstrong DG, Jude EB (2002) The role of matrix metalloproteinases in wound healing. J Am Podiatr Med Assoc 92:12–18CrossRefPubMed Armstrong DG, Jude EB (2002) The role of matrix metalloproteinases in wound healing. J Am Podiatr Med Assoc 92:12–18CrossRefPubMed
11.
Zurück zum Zitat Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839CrossRefPubMed Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839CrossRefPubMed
12.
Zurück zum Zitat Minabe M, Kodama T, Kogou T, Tamura T, Hori T, Watanabe Y, Miyata T (1989) Different crosslinked types of collagen implanted in rat palatal gingiva. J Periodontol 60:35–43CrossRefPubMed Minabe M, Kodama T, Kogou T, Tamura T, Hori T, Watanabe Y, Miyata T (1989) Different crosslinked types of collagen implanted in rat palatal gingiva. J Periodontol 60:35–43CrossRefPubMed
13.
Zurück zum Zitat Golub LM, McNamara TF, D’Angelo G, Greenwald RA, Ramamurthy NS (1987) A non-antimicrobial chemically modified tetracycline inhibits mammalian collagenase activity. J Dent Res 66:1310–1314CrossRefPubMed Golub LM, McNamara TF, D’Angelo G, Greenwald RA, Ramamurthy NS (1987) A non-antimicrobial chemically modified tetracycline inhibits mammalian collagenase activity. J Dent Res 66:1310–1314CrossRefPubMed
14.
Zurück zum Zitat Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T (1998) Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv Dent Res 12:12–26CrossRefPubMed Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T (1998) Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv Dent Res 12:12–26CrossRefPubMed
15.
Zurück zum Zitat Greenwald RA, Golub LM, Ramamurthy NS, Chowdhury M, Moak SA, Sorsa T (1998) In vitro sensitivity of the three mammalian collagenases to tetracycline inhibition: relationship to bone and cartilage degradation. Bone 22:33–38CrossRefPubMed Greenwald RA, Golub LM, Ramamurthy NS, Chowdhury M, Moak SA, Sorsa T (1998) In vitro sensitivity of the three mammalian collagenases to tetracycline inhibition: relationship to bone and cartilage degradation. Bone 22:33–38CrossRefPubMed
16.
Zurück zum Zitat Moses O, Nemcovsky CE, Tal H, Zohar R (2001) Tetracycline modulates collagen membrane degradation in vitro. J Periodontol 72:1588–1593CrossRefPubMed Moses O, Nemcovsky CE, Tal H, Zohar R (2001) Tetracycline modulates collagen membrane degradation in vitro. J Periodontol 72:1588–1593CrossRefPubMed
17.
Zurück zum Zitat Zohar R, Nemcovsky CE, Artzi Z, Kebudi E, Tal H, Moses O (2004) Tetracycline inhibits collagen membrane degradation in-vivo in a dose-dependent manner. J Periodontol 75:1096–1101CrossRefPubMed Zohar R, Nemcovsky CE, Artzi Z, Kebudi E, Tal H, Moses O (2004) Tetracycline inhibits collagen membrane degradation in-vivo in a dose-dependent manner. J Periodontol 75:1096–1101CrossRefPubMed
18.
Zurück zum Zitat Yang C, Zhu P, Yan L, Chen L, Meng R, Lao G (2009) Dynamic changes in matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase1 levels during wound healing in diabetic rats. J Am Podiatr Med Assoc 99:489–496CrossRefPubMed Yang C, Zhu P, Yan L, Chen L, Meng R, Lao G (2009) Dynamic changes in matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase1 levels during wound healing in diabetic rats. J Am Podiatr Med Assoc 99:489–496CrossRefPubMed
19.
Zurück zum Zitat Eliezer M, Nemcovsky C, Romanos G, Kozlovsky A, Tal H, Kolerman R, Weinreb M, Moses O (2013) Opposing effects of diabetes and tetracycline on the degradation of collagen membranes in rats. J Periodontol 84:529–534CrossRefPubMed Eliezer M, Nemcovsky C, Romanos G, Kozlovsky A, Tal H, Kolerman R, Weinreb M, Moses O (2013) Opposing effects of diabetes and tetracycline on the degradation of collagen membranes in rats. J Periodontol 84:529–534CrossRefPubMed
20.
Zurück zum Zitat Pfeiffer A, Schatz H (1995) Diabetic microvascular complications and growth factors. Exp Clin Endocrinol Diabetes 103:7–14CrossRefPubMed Pfeiffer A, Schatz H (1995) Diabetic microvascular complications and growth factors. Exp Clin Endocrinol Diabetes 103:7–14CrossRefPubMed
21.
Zurück zum Zitat Schmidt AM, Yan SD, Brett J, Mora R, Nowygrod R, Stern D (1993) Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products. J Clin Invest 91:2155–2168CrossRefPubMedPubMedCentral Schmidt AM, Yan SD, Brett J, Mora R, Nowygrod R, Stern D (1993) Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products. J Clin Invest 91:2155–2168CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Radoff S, Vlassara H, Cerami A (1988) Characterization of a solubilized cell surface binding protein on macrophages specific for proteins modified nonenzymatically by advanced glycosylated end products. Arch Biochem Biophys 263:418–423CrossRefPubMed Radoff S, Vlassara H, Cerami A (1988) Characterization of a solubilized cell surface binding protein on macrophages specific for proteins modified nonenzymatically by advanced glycosylated end products. Arch Biochem Biophys 263:418–423CrossRefPubMed
23.
Zurück zum Zitat Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580CrossRefPubMed Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580CrossRefPubMed
24.
Zurück zum Zitat Yamagishi S, Ueda S, Matsui T, Nakamura K, Okuda S (2008) Role of advanced glycation end products (AGEs) and oxidative stress in diabetic retinopathy. Curr Pharm Des 14:962–968 ReviewCrossRefPubMed Yamagishi S, Ueda S, Matsui T, Nakamura K, Okuda S (2008) Role of advanced glycation end products (AGEs) and oxidative stress in diabetic retinopathy. Curr Pharm Des 14:962–968 ReviewCrossRefPubMed
25.
Zurück zum Zitat Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, Liou GI, Caldwell RW (2005) Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr Drug Targets 6:511–524CrossRefPubMed Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, Liou GI, Caldwell RW (2005) Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr Drug Targets 6:511–524CrossRefPubMed
26.
Zurück zum Zitat Schwarz F, Rothamel D, Herten M, Sager M, Becker J (2006) Angiogenesis pattern of native and cross-linked collagen membranes: an immunohistochemical study in the rat. Clin Oral Implants Res 17(4):403–409CrossRefPubMed Schwarz F, Rothamel D, Herten M, Sager M, Becker J (2006) Angiogenesis pattern of native and cross-linked collagen membranes: an immunohistochemical study in the rat. Clin Oral Implants Res 17(4):403–409CrossRefPubMed
27.
Zurück zum Zitat Han SY, Jee YH, Han KH, et al. (2006) An imbalance between matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 contributes to the development of early diabetic nephropathy. Nephrol Dial Transplant 21:2406–2416CrossRefPubMed Han SY, Jee YH, Han KH, et al. (2006) An imbalance between matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 contributes to the development of early diabetic nephropathy. Nephrol Dial Transplant 21:2406–2416CrossRefPubMed
28.
Zurück zum Zitat Tesch GH (2007) Role of macrophages in complications of type 2 diabetes. Clin Exp Pharmacol Physiol 34:1016–1019CrossRefPubMed Tesch GH (2007) Role of macrophages in complications of type 2 diabetes. Clin Exp Pharmacol Physiol 34:1016–1019CrossRefPubMed
30.
Zurück zum Zitat Hoben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580CrossRef Hoben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580CrossRef
31.
Zurück zum Zitat Hammes HP, Lin J, Bretzel RG, Brownlee M, Breier G (1998) Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. Diabetes 47:401–406CrossRefPubMed Hammes HP, Lin J, Bretzel RG, Brownlee M, Breier G (1998) Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. Diabetes 47:401–406CrossRefPubMed
33.
Zurück zum Zitat Nakagawda T, Sato W, Kosugi T, Johnson RJ (2013) Uncoupling of VEGF with endothelial NO as a potential mechanism for abnormal angiogenesis in the diabetic nephropathy. J Diabetes Res 2013:184539 Nakagawda T, Sato W, Kosugi T, Johnson RJ (2013) Uncoupling of VEGF with endothelial NO as a potential mechanism for abnormal angiogenesis in the diabetic nephropathy. J Diabetes Res 2013:184539
34.
Zurück zum Zitat Tilton RG (2002) Diabetic vascular dysfunction: links to glucose-induced reductive stress. Micros Res Tech. 57:390–407CrossRef Tilton RG (2002) Diabetic vascular dysfunction: links to glucose-induced reductive stress. Micros Res Tech. 57:390–407CrossRef
35.
Zurück zum Zitat Mathews MK, Merges C, McLeod DS, Lutty GA (1997) Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy. Invest Ophthalmol Vis Sci 38:2729–2741PubMed Mathews MK, Merges C, McLeod DS, Lutty GA (1997) Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy. Invest Ophthalmol Vis Sci 38:2729–2741PubMed
36.
Zurück zum Zitat Osaadon P, Fagan XJ, Lifshitz T, Levy J (2014) A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye (Lond) 28:510–520CrossRef Osaadon P, Fagan XJ, Lifshitz T, Levy J (2014) A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye (Lond) 28:510–520CrossRef
37.
Zurück zum Zitat Unlü F, Güneri PG, Hekimgil M, Yeşilbek B, Boyacioğlu H (2003) Expression of vascular endothelial growth factor in human periodontal tissues: comparison of healthy and diabetic patients. J Periodontol 74:181–187CrossRefPubMed Unlü F, Güneri PG, Hekimgil M, Yeşilbek B, Boyacioğlu H (2003) Expression of vascular endothelial growth factor in human periodontal tissues: comparison of healthy and diabetic patients. J Periodontol 74:181–187CrossRefPubMed
38.
Zurück zum Zitat Carmeli E, Kodesh E, Nemcovsky CE (2009) Tetracycline therapy for muscle atrophy due to immobilization. J Musculoskelet Neuronal Interact 9:81–88PubMed Carmeli E, Kodesh E, Nemcovsky CE (2009) Tetracycline therapy for muscle atrophy due to immobilization. J Musculoskelet Neuronal Interact 9:81–88PubMed
39.
Zurück zum Zitat Golub LM, Ramamurthy NS, McNamara TF, Greenwald RA, Rifkin BR (1991) Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit Rev Oral Biol Med 2:297–321PubMed Golub LM, Ramamurthy NS, McNamara TF, Greenwald RA, Rifkin BR (1991) Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit Rev Oral Biol Med 2:297–321PubMed
40.
Zurück zum Zitat Ramamurthy NS, Vernillo AT, Greenwald RA, Lee HM, Sorsa T, Golub LM, Rifkin BR (1993) Reactive oxygen species activate and tetracyclines inhibit rat osteoblast collagenase. J Bone Miner Res 8:1247–1253CrossRefPubMed Ramamurthy NS, Vernillo AT, Greenwald RA, Lee HM, Sorsa T, Golub LM, Rifkin BR (1993) Reactive oxygen species activate and tetracyclines inhibit rat osteoblast collagenase. J Bone Miner Res 8:1247–1253CrossRefPubMed
Metadaten
Titel
Accelerated degradation of collagen membranes in diabetic rats is associated with increased infiltration of macrophages and blood vessels
verfasst von
Ofer Moses
Meizi Eliezer
Carlos Nemcovsky
Haim Tal
Miron Weinreb
Publikationsdatum
06.11.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Oral Investigations / Ausgabe 7/2016
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-015-1635-9

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