Research Interests:
1) Disease Pathogenesis
Epithelial cells play a critical role in maintaining systemic health because they provide a functional barrier that separates the external environment from the host. Intraorally this barrier is equally important and very challenging to maintain for two significant reasons. Tissues lie in close proximity to a biofilm of bacteria (dental plaque) that is often present and the epithelial tissues that do lie in close proximity to teeth do not establish a strong barrier at the best of times. Therefore, bacterial components are able to penetrate the epithelial layers and stimulate the underlying connective tissues to express growth factors that may in turn specifically stimulate local epithelial cell proliferation and migration. This may support the formation of pocket epithelium and is a major hallmark of periodontal disease onset and progression. In addition, rapid and excessive proliferation and migration of epithelium during post surgical wound healing limits the amount of periodontal regeneration that is achieved.
Currently my laboratory has focused it work on the regulation, expression and function of paracrine mediated epithelial-specific growth factors. These growth factors are called Keratinocyte Growth Factors-1, and –2 but are also designated as Fibroblast Growth Factors-7 and –10, respectively. Regulators of their expression and the function that they may play in stimulating epithelial cell proliferation, migration and survival are being examined. This increase in proliferation and migration may in fact contribute to some of the histological features seem during the onset of periodontal diseases and may support the formation of pocket epithelium. In addition, understanding key mechanisms that regulate epithelial cell migration and proliferation may lead to alternate strategies that can be used to regulate these cellular processes during wound healing. A key step required to improve periodontal regeneration.
2) Periodontal Regeneration using Mesenchymal Stem Cells (MSC)
The laboratory is beginning to explore the potential of using bone marrow MSC to regenerate lost periodontal attachment. This is being explored in in vitro and in vivo animal models.
Research Project Information:
- Function of an epithelial-specific growth factor (KGF) during chronic inflammation
- Periodontal Regeneration using bone marrow mesenchymal stem cells (MSC)
Refereed Publications (* = significant)
(a) Journals
Putnins, E.E., Lavelle, C.L.B. and Holthuis, A. (1988). Detection of three-walled infrabony defects by Subtraction Radiography. Oral Surg., Oral Med. and Oral Pathol. 65:102-108.
* Putnins, E.E. and Bowden, G.H. (1993). Antigenic relationships between oral Actinomyces isolates, Actinomyces naeslundii genospecies 1 and 2, Actinomyces howellii, Actinomyces denticolens and Actinomyces slackii. J. Dent. Res. 72:1374-1385.
* Putnins, E.E., Firth, J.D. and Uitto, V.-J. (1995). Keratinocyte growth factor stimulation of gelatinase (MMP-9) and plasminogen activator (uPA) in histiotypic epithelial cell culture. J. Invest. Derm. 104:989-994.
* Putnins, E.E., Firth, J.D. and Uitto, V.-J. (1996). Stimulation of collagenase (MMP-1) synthesis in histiotypic epithelial cell culture by heparin and heparan sulfate with further stimulation by KGF. Matrix Biology, 15:21-29.
Firth, J.D., Sue, E.S., Putnins, E.E., Oda, D. and Uitto, V.-J. (1996). Chymotrypsin-like enzyme secretion is stimulated in cultured epithelial cells during proliferation and in response to Actinobacillus Actinomycetemcomitans. J. Periodont. Res. 31:345-354.
Firth, J.D., Putnins, E.E., Larjava, H., and Uitto, V.-J. (1997). Bacterial Phospholipase C Upregulates Matrix Metalloproteinase Expression by Cultured Epithelial Cells. Infection and Immunity 65:4931-4936.
Uitto, V.-J., Airola, K., Vaalamo, M., Johansson, N., Putnins, E.E., Firth, J.D., Salonen, J., Lopez-Otin, C., Saarialho-Kere, U. and Kahari, V.-M. (1998). Collagenase-3 (Matrix Metalloproteinase-13) Expression is Induced in Oral Mucosal Epithelium During Chronic Inflammation. Am. J. Pathol. 152:1489-1499.
* Putnins, E.E., Firth, J.D., Lohachitranont, A., Uitto, V.-J. and Larjava, H. (1999). Keratinocyte Growth Factor (KGF) Promotes Keratinocyte Cell Attachment and Migration on Collagen and Fibronectin. Cell Adhes. Commun. 7(3):211-221.
Putnins, E.E. (1999). Dental Unit Waterline Contamination: Evolving Issues? J. Can. Dent. Assoc. 65:629-632.
* Noce, L., Di Giovanni, D. and Putnins, E.E. (2000). An Evaluation of the Heterotrophic Plate Count Laboratory and Sampling Procedures and their Effects on Perceived Dental Unit Waterline Contamination. J. Can. Dent. Assoc. 66:262
Wiebe, C.B. and Putnins, E.E. (2000). The periodontal disease classification system of the American Academy of Periodontology–an update. Journal of the Canadian Dental Association 66(11):594-597.
* Putnins, E.E., Di Giovanni, D. and Bhullar, A. (2001). Dental Unit Waterline Contamination and Its Possible Implications During Periodontal Surgery. Journal of Periodontology 72:393-400.
Firth, J.D., Putnins, E.E., Larjava, H. and Uitto, V.-J. (2001). Exogenous phospholipase C stimulates epithelial cell migration and integrin expression in vitro. Wound Repair and Regeneration 9(2):86-94.
Wiebe, C., Adkins, C., Putnins, E.E., Häkkinen, L. and Larjava, H. (2001). Naturally Occurring Periodontal Bone Loss in the Wild Deer Mouse, genus Peromyscus. Journal of Periodontology 72:620-625.
Wiebe, C.B., Häkkinen, L., Putnins, E.E., Walsh, P. and Larjava, H. (2001). Successful Periodontal Maintenance of a Case with Papillon-Lefevre Syndrome: 12 Year Follow-up and Review of the Literature. Journal of Periodontology 72:824-830.
* Sanaie, A.R., Firth, J.D., Uitto, V.-J. and Putnins, E.E. (2002). Keratinocyte Growth Factor (KGF)-1 and -2 Protein and Gene Expression in Human Gingival Fibroblasts. Journal of Periodontal Research 37(1):66-74.
Putnins, E.E., Sanaie, A.R., Wu, Q. and Firth, J.D. (2002). Induction of Keratinocyte Growth Factor-1 Expression by Lipopolysaccharide is Regulated by CD14 and Toll-like Receptors 2 and 4. Infection and Immunity, 70(12):6541-6548.
Wiebe, C.B., Penagos, H., Luong, N., Slots, J., Epstein, E. Jr., Siegel, D., Häkkinen, L., Putnins, E.E. and Larjava, H.S. (2003). Clinical and Microbiologic Study of Periodontitis Associated with Kindler Syndrome. Journal of Periodontology, 74(1):25-31.
Firth, J.D. and Putnins, E.E. (2004) Keratinocyte Growth Factor-1 Inhibits Wound Edge Epithelial Cell Apoptosis in Vitro. Journal of Investigative Dermatology, 122(1):222-231.
Uitto, V.-J., Bailley, D., Wu, Q., Gendron, R., Grenier, D., Putnins, E.E.,Karnervo, A. and Firth, J.D. (2005) Fusobacterium nucleatum increases collagenase-3 production and migration of epithelial cells. Infect Immun 73(2):1171-1179.
Li, M., Firth, J.D. and Putnins, E.E. (2005). Keratinocyte Growth Factor-1 Expression in Healthy and Diseased Human Periodontal Tissues. Journal of Periodontal Research 40:118-128.
Ekuni, D., Firth, J.D. and Putnins, E.E. (2005). RNA Integrity and in situ RT-PCR in Dento-alveolar Tissues After Microwave Accelerated Demineralization. Archives of Oral Biology, in press.
(b) Abstracts
Putnins, E.E. and Bowden, G.H.W. (1988). Composition of the carbohydrate antigens of Actinomyces. Canadian Academy of Periodontology.
Putnins, E.E. and Bowden, G.H.W. (1990). Protein antigens from cell walls and cell extracts of Actinomyces. J. Dent. Res. 69:254.
Putnins, E.E. and Bowden, G.H.W. (1991). Antigenic cross reactivity between Actinomyces viscosus and Actinomyces naeslundii. J. Dent. Res. 70 Special Issue: 415.
Pan, Y.-M., Firth, J., Putnins, E.E. and Uitto, V.-J. (1993). Matrix metalloproteinases of periodontal epithelial cells. J. Dent. Res. 72 Special Issue: 271.
Uitto, V.-J., Firth, J. Pan, Y.-M. and Putnins, E.E. (1993). Effect of epidermal growth factor on epithelial cell matrix metalloproteinase expression. J. Cell. Biochem. Supplement 17E: 134.
Firth, J.D., Uitto, V.-J., Pan, Y.-M. and Putnins, E.E. (1994). Exogenous Phospholipase C induction of epithelial matrix metalloproteinases. J. Dent. Res. 73 Special Issue: 161.
Putnins, E.E. and Uitto, V.-J. (1994). Induction of periodontal ligament epithelial cell proteases by keratinocyte growth factor. J. Dent. Res. 73 Special Issue: 379.
Putnins, E.E., Firth, J.D. and Uitto, V.-J. (1995). Induction of epithelial cell collagenase by keratinocyte growth factor and heparin. J. Dent. Res. 74 Special Issue: 81.
Firth, J.D., Uitto, V.-J., Putnins, E.E. and Oda, D. (1996). Stimulated chrymotrypsin secreted by proliferating epithelia cells. J. Dent. Res. 74 Special Issue:103.
Uitto, V.-J., Firth, J.D., Sue, E.S. and Putnins, E.E. (1996). Neutral proteinase secretion is stimulated in cultured epithelial cells during proliferation and migration, Key Stone Symposia-Cell Migration: 309.
Firth, J.D., Putnins, E.E., Larjava, H.S. and Uitto, V.-J. (1997). Bacterial PLC enhances epithelial migration, inhibits proliferation. J. Dent. Res. 76 Special Issue: 360.
Putnins, E.E., Lohachitranont, S., Firth, J.D. and Larjava, H.S. (1997). Role of ECM proteins in modulating KGF-induced epithelial migration. J. Dent. Res. 76 Special Issue: 360.
Uitto, V.-J., Airola, K., Vaalamo, M., Johansson, N., Putnins, E.E., Firth, J.D., Salonen, J., Lopez-Otin, C., Saarialho-Kere, U. and Kahari, V.-M. (1998). Matrix Metalloproteinase-13 is a major collagenase in inflamed human gingiva. J. Dent. Res. 77 Special Issue: 994.
Firth, J.D., Putnins, E.E., Larjava, H.S. and Uitto, V.-J. (1999). Bacterial PLC alters epithelial integrin expression and localization. J. Dent. Res. 78 Special Issue: 536.
Putnins, E.E., Di Giovanni, D. and Bhullar, A. (1999). Evaluation of general dental water quality in relationship to surgery. J. Dent. Res. 78 Special Issue: 536.
Putnins, E.E., Noce, L. and Di Giovanni, D. (1999). Evaluation of the heterotrophic plate count laboratory methods. J. Dent. Res. 78 Special Issue: 262.
Putnins, E.E., Firth, J.D., Uitto, V.-J. and Larjava, H.S. (1999). Keratinocyte growth factor promotes keratinocyte cell attachment and migration. J. Dent. Res. 78 Special Issue: 262.
Wiebe, C.B., Putnins, E.E. and Larjava, H.S. (2000). Spontaneous periodontal bone loss in the wild deer mouse Peromyscus. J. Dent. Res. 79 Special Issue: 578.
Firth, J.D., MacDonald, H.M., Sanaie, A.R. and Putnins, E.E. (2000). Keratinocyte growth factor expression by gingival fibroblasts. J. Dent. Res. 79 Special Issue: 620.
Putnins, E.E., Sanaie, A.R., Firth, J.D. and Wu, Q. (2002). CD14 and Toll-like receptors regulate lipopolysaccharide induction of KGF-1 protein expression. J. Dent. Res. 81 Special Issue A: A-232.
Putnins, E.E. (2002). LPS and proinflammatory cytokines stimulate gingival fibroblast expression of KGF-1 (FGF-7): An epithelial specific growth factor. Eur. J. Physiol. 444:R56.
Firth, J.D. and Putnins, E.E. (2003) KGF-1 Inhibits Wound Edge Epithelial Cell Apoptosis. Wound Repair Regen., 11(2):A9.
Putnins, E.E. and Li, M. (2003) Localization of KGF-1 Protein Expression in Oral Gingival Tissues. Wound Repair Regen., 11(2):A32.ngivasl
Li, M., Firth, J.D., and Putnins, E.E. (2004) KGF-1 Expression in Healthy and Diseased Human Gingival Tissues. J. Dent Res. Published.
Book Chapters
Putnins, E.E. (2001) Keratinocyte Growth Factor (KGF): Its Possible Use in Tissue Engineering. In: Cultured Human Keratinocytes and Tissue Engineered Skin Substitutes – State of the Art. R.E. Horch, A.M. Munster and B. Achauer, Editors, pp. 129-138.