Dr. Hannu S. Larjava

Research Interest:

Integrins and Proteoglycans in Periodontal Tissues

Cell adhesion to extracellular matrix proteins and to each other is mediated by cell surface receptors called integrins. Other extracellular matrix and cell surface-associated molecules, such as proteoglycans, also participate in regulating cell adhesion. Maintenance of normal tissue architecture as well as wound healing and tumor cell invasion are critically dependent on the proper function of these molecules. For example, adhesion of the junctional epithelium attaching the gingival tissue to the tooth enamel is mediated by integrins on the surface of epithelial cells. During healing of skin and periodontal wounds, integrins play a fundamental role in the cell-migration process of both epithelial cells and fibroblasts. My laboratory is interested in finding out the expression profiles, function and regulation of integrins and proteoglycans in periodontal tissues and cells during normal tissue maintenance, inflammation and wound healing.

Research Themes:

Selected Publications:

Uitto V-J, Nieminen A, Coil J, Hurttia H, Larjava H: Oral fluid elastase as an indicator of periodontal health. J Clin Periodontol 23: 30-37, 1996.

Haapasalmi K, Zhang K, Tonnesen M, Olerud J, Sheppard D, Salo T, Kramer R, Clark RAF, Uitto V-J, Larjava H: Keratinocytes in human wounds express avß6 integrin. J Invest Dermatol 106: 42-48, 1996

Wiebe CB, Silver JG, Larjava HS: Early onset periodontitis associated with Weary-Kindler syndrome. A case report. J Periodontol 67: 1004-1010, 1996

Häkkinen L, Westermarck J, Kähäri V-M, Larjava H: Human granulation tissue fibroblasts show enhanced proteoglycan gene expression and an altered response to TGFß1. J Dent Res 75:1767-1778,1996

Oksala O, Haapasalmi K, Häkkinen L, Uitto V-J, Larjava H: Expression of heparan sulphate and small dermatan/chondroitin sulphate proteoglycans in chronically inflamed human periodontium. J Dent Res 76:1250-1259, 1997.

Firth JD, Pan Y-M, Putnins EE, Larjava H, Uitto V-J: Effect of bacterial phospholipase C onmatrix metalloproteinase expression and cell migration of cultured epithelial cells. Infect Immun, 65: 4931-4936, 1997.

Kainulainen T, Häkkinen L, Hamidi S, Larjava K, Kallioinen M, Peltonen J, Salo T, Larjava H, Oikarinen A: Essential role of laminin-5 during re-epithelialization of wounds. J Histochem Cytochem, 46: 353-360, 1998.

Tjäderhane L, Salo T, Sorsa T, Uitto V-J, Larmas M, Larjava H: The activation and function of matrix metalloproteinases in dentin matrix breakdown in caries lesioins. J Dent Res, 77: 1622-1629, 1998.

Tjäderhane L, Salo T, Larjava H, Larmas M, Overall CM: A novel organ culture method to study the function of the human odontoblasts in vitro: gelatinase expression by odontoblasts is differentially regulated by TGF-ß1. J Dent Res 77: 1486-1496,1998.

Mäkelä M, Salo T, Larjava H: MMP-9 from TNF(-stimulated keratinocytes binds to cell surface and type I collagen. Biochem Biophys Res Commun 253: 325-335, 1998.

Mäkelä M, Uitto V-J, Sorsa T, Salo T, Teronen O, Larjava H: The effects of chemically modified tetracyclines (CMTs) on human keratinocyte proliferation and migration. Adv Dent Res, 12: 131-135, 1998.

Wiebe CB and Larjava H: Abnormal deposition of type VII collagen in Kindler syndrome. Arch Dermatol Res, 291:6-13, 1999

Häkkinen L, Kainulainen T, Salo T, Grenman R, Larjava H: Expression of integrin (9 subunit and tenascin in oral leukoplakia, lichen planus and squamous cell carcinoma. Oral Diseases, 5: 210-217, 1999.

Mäkelä M, Larjava H, Pirila E, Maisi P, Salo T, Sorsa T, Uitto V-J: Matrix metalloproteinase 2 (gelatinase A) is related to migration of keratinocytes. Exp Cell Res, 251: 67-78, 1999.

Koivisto L, Larjava K, Hakkinen L, Uitto V-J, Heino J, Larjava H: Different integrins mediate cell spreading, haptotaxis and lateral migration of HaCat keratinocytes on fibronectin. Cell Adhesion and Communication, 7: 245-257, 1999

Putnins EE, Firth JD, Lohachitranont A, Uitto V-J, Larjava H: Keratinocyte growth factor (KGF) promotes keratinocyte cell attachment and migration on collagen and fibronectin. Cell Adhesion and Communication, 7:211-221, 1999.

Ravanti L, Häkkinen L, Larjava H, Saarialho-Kere U, Foschi M, Han J, Kähäri V- M: Transforming Growth Factor-ß Induces Collagenase-3 (MMP-13) Expression by Human Gingival Fibroblasts via p38 Mitogen-activated Protein Kinase. J Biol Chem 274: 37292-37300, 1999

Pauletto N, Larjava H, Uitto V-J: Effect of cigarette smoking on oral elastase activity in adult periodontitis patients. J Periodont 71:58-62, 2000

Koivisto L, Grenman R, Heino J, Larjava H: Integrins (5ß1, (vß1 and (vß6 collaborate in squamous carcinoma cell spreading and migration on fibronectin. Exp Cell Res 255:10-17, 2000

Häkkinen L, Hildebrand C, Berndt A, Kosmehl H, Larjava H: Immunolocalization of tenascin-C, (9 integrin subunit and (vß6 integrin during wound healing in human oral mucosa. J Histochem Cytochem 48:985-998, 2000

Häkkinen L, Strassburger S, Scott P, Kähäri V-M, Eichstetter I, Iozzo RV, Larjava H: A role for decorin in the structural organization of periodontal ligament. Lab Invest 80:1869-1880, 2000

Hamidi S, Salo T, Kainulainen T, Epstein J, Lerner K, Larjava H: Expression of (vß6 integrin in oral leukoplakia. British J Cancer 82:1433-1440, 2000

Wiebe CB, Adkins CA, Putnins EE, Häkkinen L, Larjava, H: Spontaneous periodontal bone loss in the wild deer mouse, genus peromyscus. J Periodontol 72:620-625, 2001

Wiebe CB, Häkkinen L, Putnins EE, Walsh P, Larjava H: Successful periodontal maintenance of a case with Papillon-Lefevre syndrome: 12 year follow-up and review of the current literature. J Periodontol 72:824-830, 2001

Firth JD, Putnins EE, Larjava H, Uitto V-J: Exogenous phospholipase C stimulates epithelial cell migration and integrin expression in vitro. Wound Rep Regen 9:86-94, 2001

Hildebrand, HC, Häkkinen L, Wiebe C, Larjava H: Characterization of organotypic keratinocyte cultures on de-epithelialized tongue mucosa. Histol Histopathol 17: 151-163, 2002

Hakkinen L, Koivisto L, Larjava H: An improved method for culture of epidermal keratinocytes from newborn mouse skin. Methods in Cell Science, 23:189-196, 2002.

Wiebe CB, Penagos H, Luong N, Slots J, Epstein E Jr, Siegel D, Häkkinen L, Putnins EP, Larjava HS. Clinical and microbiologic study of periodontitis associated with kindler Syndrome. J Periodontol, 74:25-31, 2003.

Koivisto L, Alavian K, Häkkinen L, McCulloch CA, Larjava H. Glycogen synthase kinase-3 regulates extended lamellipodia formation in human keratinocytes. J Cell Science, 116:3749-3760, 2003.

Impola U, Uitto V-J, Hietanen J, Häkkinen L, Zhang L , Larjava H, and Saarialho-Kere U. Differential expression of matrilysin-1 (MMP-7), 92 kDa gelatinase (MMP-9) and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer. J. Pathol, 202:14-22, 2004.

Häkkinen L, Koivisto L, Gardner H, Saarialho-Kere, U, Carroll J, Lakso M, Heino J, Larjava, H. Increased expression of beta-6 integrin in skin leads to spontaneous development of chronic wounds. Am J Pathol, 164:229-242, 2004.

Koivisto L, Häkkinen L, Matsumoto K, McCulloch CA, Yamada K, Larjava H. Glycogen synthase kinase-3 regulates cytoskeleton and translocation of Rac1 in long cellular extensions in human keratinocytes. Exp Cell Res, 293:68-80, 2004.

Jokinen J, Dadu E, Nykvist P, Käpylä J, White DJ, Ivaska J, Vehviläinen P, Reunanen H, Larjava H, Häkkinen L, Heino J. Integrin-mediated cell adhesion to type 1 collagen fibrils. J Biol Chem, 279:31956-31963, 2004.

Alimohamad H, Habijanac T, Larjava H, Häkkinen L. Colocalization of the collagen-binding proteoglycans decorin, biglycan, fibromodulin, and lumican with different cells in human gingiva. J Periodont Res, 40:73-86, 2005.

Matheson S, Larjava H, Häkkinen L. Distinctive localization and function for lumican, fibromodulin and decorin to regulate collagen fibril organization in periodontal tissues. J Periodont Res, 40:312-324, 2005.

Bhide VM, Laschinger CA, Arora PD, Lee W, Häkkinen L, Larjava H, Sodek J, McCulloch CAG. Collagen phagocytosis by fibroblasts is regulated by decorin. J Biol Chem, 280:23103-23113, 2005.

Tsang P, Derkson G, Priddy R, Junker AK, Slots J, Larjava H. Severe periodontitis in a 5-year-old girl with hyperimmunoglobulin E syndrome. Pediatr Dent 27:68-73, 2005.

Scientific Reviews

Larjava H, Haapasalmi K, Salo T, Wiebe C, Uitto V-J: Keratinocyte integrins in wound healing and chronic inflammation of the human periodontium. Oral Diseases, 2: 77-86, 1996

Pauletto N, Silver JG and Larjava H: Nonsteroidal anti-inflammatory agents: potential modifiers of peridontal disease progression. J Canadian Dent Assoc, 63: 824-832, 1997.

Wiebe CB and Larjava H: Do mutations in the basement membrane zone affect the human periodontium: review with special reference to epidermolysis bullosa. Periodontal Abstracts 46: 5-18, 1998.

Donnelly L, Larjava H, Craig BJ: A rationale to combining chlorhexidine and fluoride. Oral Health, November, pp. 31-39, 2000

Häkkinen L, Uitto V-J, Larjava H: Cell biology of gingival wound healing. Periodontology 24:127-152, 2000

Hildebrand HC, Epstein J, Larjava H: The influence of psychological stress on periodontal disease. J West Soc Periodontol Periodontal Abstr 48(3):69-77, 2000

Larjava H, Koivisto L, Häkkinen L: Keratinocyte interactions with the fibronectin during wound healing. In Cell Invasion, Eds Heino J, Kahari V-M, Landes Bioscience, in press, 2002

Steffensen B, Häkkinen L, Larjava H: Proteolytic events of wound healing – coordinated interaction between matrix metalloproteinases (MMPs), integrins, and extracellular matrix molecules. Crit Rev Oral Biol Med, 12:373-398, 2002.