Intraarticular induction of interleukin-1β expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain
Yu-Ching Lai
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorSolomon S. Shaftel
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorJen-nie H. Miller
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorRoss H. Tallents
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorYoon Chang
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorCarl A. Pinkert
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorJohn A. Olschowka
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorIan M. Dickerson
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorJ. Edward Puzas
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorM. Kerry O'Banion
University of Rochester School of Medicine & Dentistry, Rochester, New York
Drs. O'Banion and Kyrkanides have applied for a patent for the nucleic acids (patent pending PCT/US2005/042058).
Search for more papers by this authorCorresponding Author
Stephanos Kyrkanides
University of Rochester School of Medicine & Dentistry, Rochester, New York
Drs. O'Banion and Kyrkanides have applied for a patent for the nucleic acids (patent pending PCT/US2005/042058).
University of Rochester Eastman Dental Center, 625 Elmwood Avenue, Rochester, NY 14620Search for more papers by this authorYu-Ching Lai
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorSolomon S. Shaftel
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorJen-nie H. Miller
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorRoss H. Tallents
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorYoon Chang
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorCarl A. Pinkert
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorJohn A. Olschowka
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorIan M. Dickerson
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorJ. Edward Puzas
University of Rochester School of Medicine & Dentistry, Rochester, New York
Search for more papers by this authorM. Kerry O'Banion
University of Rochester School of Medicine & Dentistry, Rochester, New York
Drs. O'Banion and Kyrkanides have applied for a patent for the nucleic acids (patent pending PCT/US2005/042058).
Search for more papers by this authorCorresponding Author
Stephanos Kyrkanides
University of Rochester School of Medicine & Dentistry, Rochester, New York
Drs. O'Banion and Kyrkanides have applied for a patent for the nucleic acids (patent pending PCT/US2005/042058).
University of Rochester Eastman Dental Center, 625 Elmwood Avenue, Rochester, NY 14620Search for more papers by this authorAbstract
Objective
To examine the effects of intraarticular induction of interleukin-1β (IL-1β) expression in adult mice.
Methods
We used somatic mosaic analysis in a novel transgenic mouse with an inducible IL-1β transcription unit. Transgene activation was induced by Cre recombinase in the temporomandibular joints (TMJs) of adult transgenic mice (conditional knockin model). The effects of intraarticular IL-1β induction were subsequently evaluated at the cellular, histopathologic, and behavioral levels.
Results
We developed transgenic mice capable of germline transmission of a dormant transcription unit consisting of the mature form of human IL-1β as well as the reporter gene β-galactosidase driven by the rat procollagen 1A1 promoter. Transgene activation by a feline immunodeficiency virus Cre vector resulted in histopathologic changes, including articular surface fibrillations, cartilage remodeling, and chondrocyte cloning. We also demonstrated up-regulation of genes implicated in arthritis (cyclooxygenase 2, IL-6, matrix metalloproteinase 9). There was a lack of inflammatory cells in these joints. Behavioral changes, including increased orofacial grooming and decreased resistance to mouth opening, were used as measures of nociception and joint dysfunction, respectively. The significant increase in expression of the pain-related neurotransmitter calcitonin gene-related peptide (CGRP) in the sensory ganglia as well as the auxiliary protein CGRP receptor component protein of the calcitonin-like receptor in the brainstem further substantiated the induction of pain.
Conclusion
Induction of IL-1β expression in the TMJs of adult mice led to pathologic development, dysfunction, and related pain in the joints. The somatic mosaic model presented herein may prove useful in the preclinical evaluation of existing and new treatments for the management of joint pathologic changes and pain, such as in osteoarthritis.
REFERENCES
- 1 Roos H, Lauren M, Adalberth T, Roos EM, Jonsson K, Lohmander S. Knee osteoarthritis after meniscectomy: prevalence of radiographic changes after twenty-one years, compared with matched controls. Arthritis Rheum 1998; 41: 687–93.
- 2 Radin EL. Protest the continuing common usage of the term osteoarthritis. Clin Orthop 1990; 263: 310–2.
- 3 Martel-Pelletier J, Alaaeddine N, Pelletier JP. Cytokines and their role in the pathophysiology of osteoarthritis. Front Biosci 1999; 4: D694–703.
- 4 Goldring MB, Suen LF, Yamin R, Lai WF. Regulation of collagen gene expression by prostaglandins and interleukin-1β in cultured chondrocytes and fibroblasts. Am J Ther 1996; 3: 9–16.
- 5 Westacott CI, Sharif M. Cytokines in osteoarthritis: mediators or markers of joint destruction? Semin Arthritis Rheum 1996; 25: 254–72.
- 6 Van de Loo A, van den Berg W. Effects of murine recombinant IL1 on synovial joints in mice: measurement of patellar cartilage metabolism and joint inflammation. Ann Rheum Dis 1990; 49: 238–45.
- 7 Pelletier JP, DiBattista JA, Roughley P, McCollum R, Martel-Pelletier J. Cytokines and inflammation in cartilage degradation. Rheum Dis Clin North Am 1993; 9: 545–68.
- 8 Evans CH, Ghivizzani SC, Robbins PD. Blocking cytokines with genes. J Leukoc Biol 1998; 64: 55–61.
- 9 Van den Berg WB, Joosten LA, van de Loo FA. TNFα and IL-1β are separate targets in chronic arthritis. Clin Exp Rheumatol 1999; 7: S105–14.
- 10 Staite ND, Richard KA, Aspar DG, Franz KA, Galinet LA, Dunn CJ. Induction of an acute erosive monarticular arthritis in mice by interleukin-1 and methylated bovine serum albumin. Arthritis Rheum 1990; 33: 253–60.
- 11 Lawlor KE, Campbell IK, O'Donnell K, Li W, Wicks IP. Molecular and cellular mediators of interleukin-1–dependent acute inflammatory arthritis. Arthritis Rheum 2001; 44: 442–50.
- 12 Ghivizzani SC, Kang R, Georgescu HI, Lechman ER, Jaffurs D, Engle JM, et al. Constitutive intra-articular expression of human IL-1β following gene transfer to rabbit synovium produces all major pathologies of human rheumatoid arthritis. J Immunol 1997; 159: 3604–12.
- 13 Stricklett PK, Nelson RD, Kohan DE. The Cre/loxP system and gene targeting in the kidney. Am J Physiol Renal Physiol 1999; 276: 651–7.
- 14 Laudanski K, Brouxhon SM, Kyrkanides S, de a Miller-Graziano C. Abnormal PGE2 regulation of monocyte TNFα levels in trauma patients parallels development of a more macrophage-like phenotype. Shock 2004; 22: 204–12.
- 15 Srinivas S, Watanabe T, Lin C, William CM, Tanabe Y, Jessell TM, et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol 2001; 1: 4–11.
- 16 Kyrkanides S, Miller JH, Brouxhon SM, Olschowka JA, Federoff HJ. β-hexosaminidase lentiviral vectors: transfer into the CNS via systemic administration. Brain Res Mol Brain Res 2005; 133: 286–98.
- 17 Lichtler A, Stover ML, Angilly J, Kream B, Rowe DW. Isolation and characterization of the rat α1(I) collagen promoter: regulation by 1,25-dihydroxyvitamin D. J Biol Chem 1989; 264: 3072–7.
- 18 Kyrkanides S, Miller JH, Bowers WJ, Federoff HJ. Transcriptional and posttranslational regulation of Cre recombinase by RU486 as the basis for an enhanced inducible expression system. Mol Ther 2003a; 8: 790–5.
- 19 Kyrkanides S, Kambylafkas P, Miller JH, Tallents RH. Non-primate lentiviral vector administration in the TMJ. J Dent Res 2004; 83: 65–70.
- 20 Kyrkanides S, Miller JH, Federoff HJ. Systemic FIV vector administration: transduction of CNS immune cells and Purkinje neurons. Brain Res Mol Brain Res 2003b; 119: 1–9.
- 21
Polites HG,
Pinkert CA.
DNA microinjection and transgenic animal production. In:
CA Pinkert, editor.
Transgenic animal technology: a laboratory handbook.
2nd ed.
San Diego:
Academic Press;
2002.
p. 15–70.
10.1016/B978-0-08-057480-6.50006-X Google Scholar
- 22 Abbott FV, Franklin KB, Conel B. The stress of a novel environment reduces formalin pain: possible role of serotonin. Eur J Pharmacol 1986; 126: 126–41.
- 23 Lund JP, Donga R, Winmer CG, Stohler CS. The pain adaptation model: a discussion of the relationship between chronic musculoskeletal and motor activity. Can J Physiol Pharmacol 1991; 69: 683–94.
- 24 Wilhelmi G, Faust R. Suitability of the C57 black mouse as an experimental animal for the study of skeletal changes due to aging, with special reference to osteo-arthrosis and its response to tribenoside. Pharmacology 1976; 14: 289–96.
- 25 Kyrkanides S, Tallents RH, Macher DJ, Olschowka JA, Stevens SY. Temporomandibular joint nociception: effects of capsaicin on substance P-like immunoreactivity in the rabbit brain stem. J Orofac Pain 2002; 16: 229–36.
- 26 Rosenblatt MI, Dickerson IM. Endoproteolysis at tetrabasic amino acid sites in procalcitonin gene-related peptide by pituitary cell lines. Peptides 1997; 18: 567–76.
- 27 Prado MA, Evans-Bain B, Oliver KR, Dickerson IM. The role of the CGRP-receptor component protein (RCP) in adrenomedullin receptor signal transduction. Peptides 2001; 22: 1773–81.
- 28 Ma W, Chabot JG, Powell KJ, Jhamandas K, Dickerson IM, Quirion R. Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems. Neuroscience 2003; 120: 677–94.
- 29 Fernihough J, Gentry C, Malcangio M, Fox A, Rediske J, Pellas T, et al. Pain related behavior in two models of osteoarthritis in the rat knee. Pain 2004; 112: 83–93.
- 30 Bandara G, Mueller GM, Galea-Lauri J, Tindal MH, Georgescu HI, Suchanek MK, et al. Intraarticular expression of biologically active interleukin-1 receptor antagonist protein by ex vivo transfer. Proc Natl Acad Sci U S A 1993; 90: 10764–8.
- 31 Hung GL, Galea-Lauri J, Mueller GM, Georgescu HI, Larkin LA, Suchanek MK, et al. Suppression of intra-articular responses to interleukin-1 by transfer of the interleukin-1 receptor antagonist gene to synovium. Gene Ther 1994; 1: 64–9.
- 32 Pinkert CA. Transgenic animal technology: alternatives in genotyping and phenotyping. Comp Med 2003; 53: 126–39.
- 33 Vos BP, Hans G, Adriaensen H. Behavioral assessment of facial pain in rats: face grooming patterns after painful and non-painful sensory disturbances in the territory of the rat's infraorbital nerve. Pain 1998; 76: 173–8.
- 34 Norsdenskiold UM, Grimby G. Grip force in patients with rheumatoid arthritis and fibromyalgia and in healthy subjects: a study with the Grippit instrument. Scand J Rheumatol 1993; 22: 14–9.
- 35 Jow RW, Clark GT. Endurance and recovery from a sustained isometric contraction of human jaw elevating muscles. Arch Oral Biol 1989; 34: 857–62.
- 36 Molin C. Vertical isometric muscle forces of the mandible: a comparative study of subjects with and without manifest mandibular pain dysfunction syndrome. Acta Odontol Scand 1972; 30: 485–99.
- 37 Stohler CS. Craniofacial pain and motor function: pathogenesis, clinical correlates, and implications. Crit Rev Oral Biol Med 1999; 10: 504–18.
- 38 Helkimo E, Carlsson GE, Yehuda C. Bite force in patients with functional disturbances of the masticatory system. J Oral Rehabil 1975; 2: 397–406.
- 39 Kehl LJ, Trempea TM, Hargreaves KM. A new animal model for assessing mechanisms and management of muscle hyperalgesia. Pain 2000; 85: 333–43.
- 40 Mao J, Coghill RC, Kellstein DE, Frenk H, Mayer DJ. Calcitonin gene-related peptide enhances substance P-induced behaviors via metabolic inhibition: in vivo evidence for a new mechanism of neuromodulation. Brain Res 1992; 74: 157–63.
- 41 Spears R, Dees LA, Sapozhnikov M, Bellinger LL, Hutchins B. Temporal changes in inflammatory mediator concentrations in an adjuvant model of temporomandibular joint inflammation. J Orofac Pain 2005; 1934–40.
- 42 Hutchins B, Spears R, Hinton RJ, Harper RP. Calcitonin gene-related peptide and substance P immunoreactivity in rat trigeminal ganglion and brain stem following adjuvant-induced inflammation of the temporomandibular joint. Arch Oral Biol 2000; 45: 335–45.
- 43 Amann R, Schuligoi R, Herzeg G, Donnerer J. Intraplantar injection of nerve growth factor into the rat hind paw: local edema and effects on thermal nociceptive threshold. Pain 1996; 64: 323–9.
- 44 Carleson J, Kogner P, Bileviciute I, Theodorsson E, Appelgren A, Appelgren B, et al. Effect of capsaicin in temporomandibular joint arthritis in rats. Arch Oral Biol 1997; 42: 869–976.
- 45 McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 1998; 393: 333–9.
- 46 Naghashpour M, Rosenblatt MI, Dickerson IM, Dahl GP. Inhibitory effect of calcitonin gene-related peptide on myometrial contractility is diminished at parturition. Endocrinology 1997; 138: 4207–14.
- 47 Kar S, Rees RG, Quirion R. Altered calcitonin gene-related peptide, substance P and enkephalin immunoreactivities and receptor binding sites in the dorsal spinal cord of the polyarthritic rat. Eur J Neurosci 1994; 6: 345–54.
- 48 Segami N, Miyamaru M, Nishimura M, Suzuki T, Kaneyama K, Murakami K. Does joint effusion on T2 magnetic resonance images reflect synovitis? II. Comparison of concentration levels of proinflammatory cytokines and total protein in synovial fluid of the temporomandibular joint with internal derangements and osteoarthrosis. Oral Surg Oral Med Oral Patholo Oral Radiol Endod 2002; 94: 515–21.
