Matrix metalloproteinases (MMPs) are important in dentinal caries, and analysis of recent data demonstrates the presence of other collagen-degrading enzymes, cysteine cathepsins, in human dentin. This study aimed to examine the presence, source, and activity of cysteine cathepsins in human caries. Cathepsin B was detected with immunostaining. Saliva and dentin cysteine cathepsin and MMP activities on caries lesions were analyzed spectrofluorometrically. Immunostaining demonstrated stronger cathepsins B in carious than in healthy dentin. In carious dentin, cysteine cathepsin activity increased with increasing depth and age in chronic lesions, but decreased with age in active lesions. MMP activity decreased with age in both active and chronic lesions. Salivary MMP activities were higher in patients with active than chronic lesions and with increasing lesion depth, while cysteine cathepsin activities showed no differences. The results indicate that, along with MMPs, cysteine cathepsins are important, especially in active and deep caries.
BenjaminIJ (2001). Matrix metalloproteinases: from biology to therapeutic strategies in cardiovascular disease. J Investig Med49:381-397.
2.
BoushellLWKakuMMochidaYBagnellRYamauchiM (2008). Immunohistochemical localization of matrixmetalloproteinase-2 in human coronal dentin. Arch Oral Biol53:109-116.
3.
BrömmeDOkamotoKWangBBBirocS (1996). Human cathepsin O2, a matrix protein-degrading cysteine protease expressed in osteoclasts. Functional expression of human cathepsin O2 in Spodoptera frugiperda and characterization of the enzyme. J Biol Chem271:2126-2132.
4.
BrownLRLefkowitzW (1966). Influences of dentinal fluids on experimental caries. J Dent Res45:1493-1498.
5.
BuckMRKarustisDGDayNAHonnKVSloaneBF (1992). Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues. Biochem J282(Pt 1):273-278.
6.
BurleighMCBarrettAJLazarusGS (1974). Cathepsin B1. A lysosomal enzyme that degrades native collagen. Biochem J137:387-398.
7.
ButtleDJ (1994). Immunopharmacology of joints and connective tissue. DaviesEMDingleJT, editors. San Diego, CA: Academic Press Inc., pp. 225-243.
8.
ByersMRLinKJ (2003). Patterns of fluoro-gold entry into rat molar enamel, dentin, and pulp. J Dent Res82:312-317.
9.
Chaussain-MillerCFiorettiFGoldbergMMenashiS (2006). The role of matrix metalloproteinases (MMPs) in human caries. J Dent Res85:22-32.
10.
DickinsonDP (2002). Cysteine peptidases of mammals: their biological roles and potential effects in the oral cavity and other tissues in health and disease. Crit Rev Oral Biol Med13:238-275.
11.
FejerskovONyvadBKiddEAM (2008). Clinical appearance of caries lesions. In: Dental caries. The disease and its clinical management. 2nd ed.Oxford, UK: Blackwell Munksgaard Ltd., pp. 7-18.
12.
HashimotoYKakegawaHNaritaYHachiyaYHayakawaTKosJ. (2001). Significance of cathepsin B accumulation in synovial fluid of rheumatoid arthritis. Biochem Biophys Res Commun283:334-339.
13.
HojoSKomatsuMOkudaRTakahashiNYamadaT (1994). Acid profiles and pH of carious dentin in active and arrested lesions. J Dent Res73:1853-1857.
14.
KafienahWButtleDJBurnettDHollanderAP (1998). Cleavage of native type I collagen by human neutrophil elastase. Biochem J330(Pt 2):897-902.
KennettCNCoxSWEleyBM (1997). Ultrastructural localization of cathepsin B in gingival tissue from chronic periodontitis patients. Histochem J29:727-734.
17.
KirschkeHKembhaviAABohleyPBarrettAJ (1982). Action of rat liver cathepsin L on collagen and other substrates. Biochem J201:367-372.
18.
KirschkeHBarrettAJRawlingsND (1995). Proteinases 1: lysosomal cysteine proteinases. Protein Profile2:1581-1643.
19.
Lauer-FieldsJLJuskaDFieldsGB (2002). Matrix metalloproteinases and collagen catabolism. Biopolymers66:19-32.
20.
LecailleFKaletaJBrommeD (2002). Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. Chem Rev102:4459-4488.
21.
LjusbergJWangYLangPNorgardMDoddsRHultenbyK. (2005). Proteolytic excision of a repressive loop domain in tartrate-resistant acid phosphatase by cathepsin K in osteoclasts. J Biol Chem280:28370-28381.
MortJSButtleDJ (1997). Cathepsin B. Int J Biochem Cell Biol29:715-720.
24.
NagaseH (1997). Activation mechanisms of matrix metalloproteinases. Biol Chem378:151-160.
25.
NguyenQMortJSRoughleyPJ (1990). Cartilage proteoglycan aggregate is degraded more extensively by cathepsin L than by cathepsin B. Biochem J266:569-573.
26.
OkamuraTShimokawaHTakagiYOnoHSasakiS (1993). Detection of collagenase mRNA in odontoclasts of bovine root-resorbing tissue by in situ hybridization. Calcif Tissue Int52:325-330.
27.
OrtegaNBehonickDStickensDWerbZ (2003). How proteases regulate bone morphogenesis. Ann NY Acad Sci995:109-116.
28.
PashleyDH (1996). Dynamics of the pulpo-dentin complex. Crit Rev Oral Biol Med7:104-133.
29.
PozganUCaglicDRozmanBNagaseHTurkVTurkB (2010). Expression and activity profiling of selected cysteine cathepsins and matrix metalloproteinases in synovial fluids from patients with rheumatoid arthritis and osteoarthritis. Biol Chem391:571-579.
30.
SeikiM (2003). Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett194:1-11.
31.
SmithAJ (2003). Vitality of the dentin-pulp complex in health and disease: growth factors as key mediators. J Dent Educ67:678-689.
32.
SteinmanRR (1985). Physiologic activity of the pulp-dentin complex. Quintessence Int16:723-726.
33.
SteinmanRRLeonoraJSinghRJ (1980). The effect of desalivation upon pulpal function and dental caries in rats. J Dent Res59:176-185.
34.
SulkalaMWahlgrenJLarmasMSorsaTTeronenOSaloT. (2001). The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats. J Dent Res80:1545-1549.
35.
SulkalaMLarmasMSorsaTSaloTTjäderhaneL (2002). The localization of matrix metalloproteinase-20 (MMP-20, enamelysin) in mature human teeth. J Dent Res81:603-607.
36.
TersariolILGeraldeliSMinciottiCLNascimentoFDPaakkonenVMartinsMT. (2010). Cysteine cathepsins in human dentin-pulp complex. J Endod36:475-481.
37.
TjäderhaneLLarjavaHSorsaTUittoVJLarmasMSaloT (1998). The activation and function of host matrix metalloproteinases in dentin matrix breakdown in caries lesions. J Dent Res77:1622-1629.
38.
TjäderhaneLSulkalaMSorsaTTeronenOLarmasMSaloT (1999). The effect of MMP inhibitor metastat on fissure caries progression in rats. Ann NY Acad Sci878:686-688.
TurkBTurkDTurkV (2000). Lysosomal cysteine proteases: more than scavengers. Biochim Biophys Acta1477:98-111.
41.
van StrijpAJJansenDCDeGrootJten CateJMEvertsV (2003). Host-derived proteinases and degradation of dentine collagen in situ. Caries Res37:58-65.
42.
YamashitaDSDoddsRA (2000). Cathepsin K and the design of inhibitors of cathepsin K. Curr Pharm Des6:1-24.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
