Dr. Lari Hӓkkinen

Research Interests:


  • Member of the Graduate Program in Cell & Developmental Biology (UBC, College for Interdisciplinary Studies)
  • Collaborator in CIHR Skin Research Training Centre (UBC, Faculty of Medicine, Department of Dermatology and Skin Science)

Selected Publications

Research Papers

  1. Häkkinen L, Yli-Urpo A, Heino J, Larjava H. Attachment and spreading of human gingival fibroblasts on potentially bioactive glasses in vitro.  J Biomed Mater Res 22:1043-1059, 1988.
  2. Larjava H, Salonen J, Häkkinen L, Närhi T. Effect of citric acid treatment on the migration of epithelium on root surfaces in vitro. J Periodontol 59:95-99, 1988.
  3. Talonpoika J, Heino J, Larjava H, Häkkinen L, Paunio K. Gingival crevicular fluid fibronectin degradation in periodontal health and disease.  Scand J Dent Res 97:415-421, 1989.
  4. Tammi R, Tammi M, Häkkinen L, Larjava H. Histochemical localization of hyaluronate in human oral epithelium using a specific hyaluronate-binding probe.  Arch Oral Biol 35:219-224, 1990.
  5. Larjava H, Häkkinen L, Rahemtulla F. A biochemical analysis of human periodontal tissue proteoglycans. Biochem J 284:267-274, 1992.
  6. Peltomäki T, Häkkinen L. Growth of the ribs at the costochondral junction in the rat.  J Anat 181:259-264, 1992.
  7. Häkkinen L, Larjava H. Characterization of fibroblast clones from periodontal granulation tissue in vitro.  J Dent Res 71:1901-1907, 1992.
  8. Häkkinen L, Oksala O, Salo T, Rahemtulla F, Larjava H. Immunohistochemical localization of proteoglycans in human periodontium.  J Histochem Cytochem 41:1689-1699, 1993.
  9. Häkkinen L, Heino J, Koivisto L, Larjava H. Altered interaction of granulation tissue fibroblasts with fibronectin is regulated by a5b1 integrin. Biochim Biophys Acta (Molecular Cell Research) 1224:33-42, 1994.
  10. Koivisto L, Heino J, Häkkinen L, Larjava H. The size of the intracellular b1 integrin precursor pool regulates the maturation of b1 integrin subunit and associated a subunits. Biochem J 300:771-779, 1994.
  11. Oksala O, Salo T, Tammi R, Häkkinen L, Jalkanen M, Inki P, Larjava H. Expression of proteoglycans and hyaluronan during wound healing.  J Histochem Cytochem 43:125-135, 1995.
  12. Kähäri V-M, Häkkinen L, Westermarck J, Larjava H. Differential regulation of decorin and biglycan gene expression by dexamethasone and retinoic acid in cultured human skin fibroblasts.  J Invest Dermatol 104:503-508, 1995. I
  13. Westermack J, Häkkinen L, Fries W, Kähäri V-M. TNF-R55-specific form of human tumor necrosis factor-a induces collagenase gene expression by human skin fibroblasts.  J Invest Dermatol 105:197-202, 1995.
  14. Häkkinen L, Kähäri V-M, Westermarck J, Larjava H. Human granulation-tissue fibroblasts show enhanced proteoglycan expression and an altered response to TGF-b1.  J Dent Res 75:1767-1778, 1996.
  15. Söderling E, Trahan L, Tammiala-Salonen T, Häkkinen L. Effects of xylitol, xylitol-sorbitol, and placebo chewing gums on the plaque of habitual xylitol consumers.  Eur J Oral Sci 105:170-177, 1997.
  16. 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.
  17. Johansson N, Westermarck J, Leppä S, Häkkinen L, Koivisto L, Lopez-Otin C, Peltonen J, Heino J, Kähäri V-M. Collagenase-3 (matrix metalloproteinase 13) gene expression by HaCaT keratinocytes is enhanced by tumor necrosis factor-a and transforming growth factor-b1.  Cell Growth Differ 8:243-250, 1997.
  18. Soukka T, Salmi M, Joensuu H, Häkkinen L, Sointu P, Koulu L, Kalimo K, Klemi P, Grenman R, Jalkanen S. Malignant transformation in squamocellular cancer is associated with downregulation of CD44v6.  Cancer Res 57:2281-2289, 1997.
  19. Kainulainen T, Häkkinen L, Hamidi S, Larjava K, Kallioinen M, Peltonen JM, Salo T, Larjava H, Oikarinen A. Essential role for laminin-5 during reepithelialization of wounds.  J Histochem Cytochem 46:353-360, 1998.
  20. Pöllänen MT, Häkkinen L, Overman DO, Salonen JI. Lactoferrin impedes epithelial cell adhesion in vitro.  J Periodontal Res 33:8-16, 1998.
  21. Häkkinen L, Westermarck J, Johansson N, Aho H, Peltonen J, Heino J, Kähäri V-M. Suprabasal expression of epidermal a2b1 and a3b1integrins in skin treated with topical retinoic acid. Br J Dermatol 138:29-36, 1998.
  22. Reunanen N, Westermarck J, Häkkinen L, Holmström T, Elo I, Eriksson J, Kähäri V-M. Enhancement of fibroblast collagenase (MMP-1) gene expression by ceramide is mediated by extracellular stimulus-regulated and stress-activated protein kinase pathways. J Biol Chem 273:5173-5145, 1998.
  23. Häkkinen L, Kainulainen T, Salo T, Sheppard D, Larjava H. Expression of integrin a9 subunit and tenascin in oral leukoplakia, lichen planus, and squamous cell carcinoma.  Oral Dis 5:210-217, 1999.
  24. Koivisto L, Larjava K, Häkkinen L, Uitto V-J, Heino J, Larjava H. Different integrins mediate cell spreading, haptotaxis and lateral migration of HaCaT keratinocytes on fibronectin.  Cell Adhes Commun 7:245-257, 1999.
  25. Ravanti L, Häkkinen L, Larjava H, Saarialho-Kere U, Fischi M, Han J, Kähäri V-M. Transforming growth factor-b induces collagenase-3 expression by human gingival fibroblasts via p38 mitogen-activated protein kinase. J Biol Chem 274:37292-37300, 1999.
  26. Häkkinen L, Hildebrand HC, Berndt A, Kosmehl H, Larjava H. Immunolocalization of tenascin-C, a9 integrin subunit and avb6 integrin during wound healing in human oral mucosa. J Histochem Cytochem 48:985-998, 2000.
  27. Rechardt O, Elomaa O, Vaalamo M, Pääkkönen K, Jahkola T, Höök-Nikanne J,Hembry RM, Häkkinen L, Kere J, Saarialho-Kere U. Stromelysin-2 (MMP-10) is upregulated during normal wound repair and is induced by cytokines. J Invest Dermatol 115:778-787, 2000.
  28. 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 80:1869-80, 2000.
  29. Wiebe CB, Adkins CA, Putnins EE, Häkkinen L, Larjava, H. Naturally occurring periodontal bone loss in the wild deer mouse, genus peromyscus. J Periodontol 72:620-625, 2001.
  30. 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.
  31. Hildebrand HC, Häkkinen L, Wiebe C, Larjava H. Characterization of organotypic keratinocyte cultures on de-epithelialized bovine tongue mucosa. Histology & Histopathology 17:151-163, 2002.
  32. Häkkinen 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.
  33. Ghersi G, Dong H., Goldstein LA, Yeh Y, Häkkinen L, Larjava HS, Chen W-T. Regulation of fibroblast migration on collagenous matrix by a cell surface peptidase complex. J Biol Chem 277:29231-29241, 2002.
  34. Leivonen S-K, Chantry A, Häkkinen L, Han J, Kähäri V-M. Smad3 mediates transforming growth factor-b-induced collagenase-3 (MMP-13) expression in human gingival fibroblasts. Evidence for cross-talk between Smad3 and p38 signaling pathways. J Biol Chem 277:46338-46, 2002.
  35. 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.
  36. Koivisto L, Alavian K, Häkkinen L, McCulloch CA, Larjava H. Glycogen synthase kinase-3 regulates formation of long lamellipodia in human keratinocytes. J Cell Science 116:3749-3760, 2003.
  37. 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 of human keratinocytes. Exp Cell Res 293:68-80, 2004.
  38. 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.
  39. Häkkinen L, Koivisto L, Gardner H, Saarialho-Kere U, Carroll JM, Lakso M, Rauvala H, Laato M, Heino J, Larjava, H. Increased expression of b6-integrin in skin leads to spontaneous development of chronic wounds. Am J Pathol 164:229-242, 2004.
  40. 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.
  41. 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 Periodontal Res 40:73-86, 2005.
  42. Matheson S, Larjava H, Häkkinen L. Distinctive localization and function for lumican, fibromodulin and decorin to regulate collagen fibril organization in periodontal tissues. J Periodontal Res 40:312-324, 2005.
  43. Leivonen S-K, Häkkinen L, Liu D, Kähäri V-M. Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate transforming growth factor-b-induced expression of connective tissue growth factor in human fibroblasts. J Invest Dermatol 124:1162-1169, 2005.
  44. 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.
  45. Aldahlawi S, Eslami A, Häkkinen L, Larjava H. The avb6 integrin plays a role in compromised epidermal wound healing. Wound Repair Regen 14:289-297, 2006.
  46. Honardoust D, Jiang G, Koivisto L, Wienke D, Isacke C, Larjava H, Häkkinen L. Expression of Endo180 is spatially and temporally regulated in distinct cells during wound healing. Histopathology 49:634-648, 2006.
  47. Koivisto L, Jiang G, Häkkinen L, Chan B, Larjava H. HaCaT keratinocyte migration is dependent on epidermal growth factor receptor signaling and glycogen synthase kinase-3alpha. Exp Cell Res, 15:2791-2805, 2006.
  48. Walsh P, Häkkinen L, Pernu H, Larjava H. Integrin expression in drug-induced gingival overgrowth. J Periodontal Res, 42:144-151, 2007.
  49. Csiszar A, Wiebe C, Larjava H, Häkkinen L. Distinct molecular composition of human interdental papilla. J Periodontol, 78:304-314, 2007.
  50. Narani N, Owen GRh, Häkkinen L, Putnins E, Larjava H. Enamel matrix proteins bind to wound provisional matrix proteins and regulate their cell adhesive properties. Eur J Oral Sci, 115:288-95, 2007.
  51. Wiebe CB, Petricca G, Häkkinen L, Jiang G, Wu C, Larjava HS. Kindler syndrome and periodontal disease: Review of the literature and 12-year follow-up of treatment outcome. J Periodontol, 79:961-966, 2008.
  52. Ghannad F, Nica D, Garcia MI, Grenier D, Johnston S, Eslami A, Koivisto L, Putnins EE, Jiang G, McKee MD, Häkkinen L, Larjava H. Absence of avb6 integrin is linked to initiation and progression of periodontal disease. Am J Pathol, 172:1271-1286, 2008.
  53. Honardoust D, Eslami A, Larjava H, Häkkinen L Localization of Small Leucine-Rich Proteoglycans and Transforming Growth Factor-b in Human Oral Mucosal Wound Healing. Wound Repair Regen, 16:814-823, 2008.
  54. Eslami A, Gallant-Behm C, Hart D, Wiebe C, Honardoust D, Gardner H, Häkkinen L, Larjava HS. Expression of Integrin avb6 and TGF-b in Scar-free vs. Scar-forming Wound Healing. J Histochem Cytochem, Jun 57:543-557, 2009.
  55. Xie Y, Gao K, Häkkinen L, Larjava H. Loss of b6 integrin partially ameliorates dexamethasone-impaired cutaneous wound healing. Wound Repair Regen, May-June 17:326-329, 2009.
  56. Petricca G, Leppilampi M, Jiang G, Owen GRh, Wiebe C, Tu Y, Koivisto L, Häkkinen L, Wu C, Larjava H. Kindlin-1 interacts with migfilin and supports keratinocyte adhesion, proliferation and migration. Eur J Oral Sci, Oct 117:516-527, 2009.
  57. Wong JW, Gallant-Behm C, Wiebe C, Mak K, Hart DA, Larjava H, Häkkinen L. Wound healing in oral mucosa results in reduced scar formation as compared to skin: Evidence from the red Duroc pig model and humans. Wound Repair Regen, Sept-Oct 17:717-729, 2009.
  58. Mak K, Manji A, Gallant-Behm CL, Wiebe C, Hart DA, Larjava H, Häkkinen L. Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model. J Dermatol Sci, Dec 56:168-180, 2009.
  59. Owen GRh, Häkkinen L, Wu C, Larjava H. Labeling antigens using preformed fluorescent molecular IgG-F(ab’)2 complexes from primary antibodies of the same species. Microsc Res Technique, Jun 73:623-30, 2010.
  60. Jacobsen JN, Steffensen B, Häkkinen L, Krogfelt KA, Larjava HS. The role of avb6-integrin in skin wound healing in diabetic mice. APMIS, Oct 118:753-764, 2010.
  61. Xie Y, McElwee JK, Owen G, Häkkinen L, Larjava HS. Integrin Beta6 Deficient Mice Show Enhanced Keratinocyte Proliferation and Retarded Hair Follicle Regression After Depilation. J Invest Dermatol; 132: 547-555, 2012.
  62. Huimin Z, Shen Y, Wang Z-J, Li L, Zheng Y-F, Häkkinen L, Haapasalo M. In vitro cytotoxicity evaluation of a novel root repair material. J Endod, 39(4):478-83, 2013.
  63. Mohazab L, Koivisto L, Jiang K, Kytömäki, L Haapasalo K, Owen GR, Wiebe C, Xie Y, Heikinheimo K, Yoshida T, Smith CE, Heino J, Häkkinen L, McKee MD Hannu Larjava. Critical role for avb6 integrin in enamel biomineralization. J Cell Sci, 126(pt 3):732-44, 2013.
  64. Mah W, Jiang G, Olver D, Cheung G, Kim B, Larjava H, Häkkinen L. Human Gingival Fibroblasts Display a Non-Fibrotic Phenotype Distinct from Skin Fibroblasts in Three-Dimensional Cultures. PLoS ONE, 9(3): e90715, 2014.
  65. Ferre FC, Larjava H, Loison Robert L-S, Berbar T, Owen GR, Berdal A, Cherifi H, Gogly B, Häkkinen L, Fournier BPJ. Formation of cartilage and synovial tissue by human gingival stem cells. Stem Cells Dev, 2014, 23(23):2895-907.
  66. Tarzemany R, Jiang G, Larjava H, Häkkinen L. Expression and function of connexin 43 in human gingival wound healing and fibroblasts. PLoS ONE 10(1): e0115524, 2015.                                                      

Review Articles

  1. Häkkinen L, Uitto V-J, Larjava H. Cell Biology of Gingival Wound Healing.  Periodontology 2000 24:127-152, 2000.
  2. Steffensen B, Häkkinen L, Larjava H. Proteolytic events of wound healing – Co-ordinated interaction among matrix metalloproteinases (MMPs), integrins, and extracellular matrix molecules.  Crit Rev Oral Biol Med 12:373-398, 2001.
  3. * Ghersi G, Dong H, Goldstein LA, Yeh Y, Häkkinen L, Larjava HS, Chen W-T Seprase-dPPIV association and prolyl peptidase and gelatinase activities of the protease complex. Adv Exp Med Biol, 524:87-94, 2003.
  4. Häkkinen L, Csiszar A. Hereditary gingival fibromatosis: Characteristics and novel putative pathogenic mechanisms. J Dent Res/Crit Rev Oral Biol Med, 86:25-34, 2007.
  5. Larjava H, Wiebe C, Gallant-Behm C, Hart DA, Heino J, Häkkinen L. Exploring scarless healing of oral soft tissues. J Can Dent Assoc, 77: b18, 2011.
  6. Larjava H, Koivisto L, Häkkinen L, Heino J. Epithelial adhesion proteins with special reference to oral epithelia. J Dent Res/Crit Rev Oral Biol Med, 90:1367-1376, 2011.
  7. Häkkinen L, Larjava H, Koivisto L. Granulation Tissue Formation and Remodeling.. Endodontic Topics, 24:94-129, 2012.
  8. Kovisto L., Larjava H, Häkkinen L. Reepithelialization of Wounds. Endodontic Topics, 24:59-93, 2012.
  9. Larjava H, Yang Y, Putnins E, Heino, J, Häkkinen L. Biological agents and cell therapies in periodontal regeneration. Endodontic Topics, 26:18–40, 2013.
  10. Koivisto L, Heino J, Häkkinen L, Larjava H. Integrins in wound healing. Advances in Wound Care, Special Edition. Chandan K. Sen, Ed. Wound Healing Society, Mary Ann Liebert Inc. publishers, USA. April 8, 2013.
  11. Fournier BPJ, Larjava H, Häkkinen L. Gingiva as a Source of Stem Cells with Therapeutic Potential. Stem Cells Dev, 22(24):3157-3177, 2013.
  12. Larjava H, Koivisto L, Heino J, Häkkinen L. Integrins in periodontal disease. Exp Cell Res, 325(2):104-110, 2014.
  13. Häkkinen L, Larjava H, Fournier BPJ. Distinct Phenotype and Therapeutic Potential of Gingival Fibroblasts. Cytotherapy, 16:1171-1186, 2014.
  14. Koivisto L, Heino J, Häkkinen L, Larjava H. Integrins in wound healing. Adv Wound Care (New Rochelle). 2014, 3(12):762-783.

Book Chapters

  1. Häkkinen L. Fibroblast-bioactive glass interactions. In: CRC Handbook of Bioactive Ceramics, Vol. I, Yamamuro, T., Hench, L.L., Wilson, J. eds., CRC Press, Inc., Boca Raton, Florida, USA, pp. 235-244, 1990.
  2. Larjava H, Koivisto L, Häkkinen L. Keratinocyte interactions with fibronectin during wound healing. In Cell Invasion (Heino J, Kähäri V-M, eds.). Landes Biosciences, Eurekah.com, Georgetown, TX, USA, pp. 42-64, 2002.
  3. Häkkinen L, Larjava H, Koivisto L. Granulation Tissue Formation and Remodeling. In Oral Wound Healing: Cell Biology and Clinical Management (ed. Larjava, H.). John Wiley & Sons, Inc., Ames, USA, pp. 125-173, 2012.
  4. Kovisto L., Larjava H, Häkkinen L. Reepithelialization of Wounds. In Oral Wound Healing: Cell Biology and Clinical Management (ed. Larjava, H.). John Wiley & Sons, Inc., Ames, USA, pp. 81-123, 2012.
  5. Larjava H., Young Y, Putnins EE, Heino J, Häkkinen L. Biological Agents and Cell therapies in Periodontal Regeneration. In Oral Wound Healing: Cell Biology and Clinical Management (ed. Larjava, H.). John Wiley & Sons, Inc., Ames, USA, pp. 262-285, 2012.
  6. Häkkinen L, Koivisto L, Heino J, Larjava H. Cell and Molecular Biology of Wound Healing. In Stem Cell Biology and Tissue Engineering in Dental Sciences. Ajaykumar Vishwakarma, Paul Sharpe, Songtao Shi, Xiu-Ping Wang and Murugan Ramalingam, Eds. Elsevier, USA. Chapter 50, pp. 669-690, 2015.