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Vet Comp Orthop Traumatol 2002; 15(02): 72-77
DOI: 10.1055/s-0038-1632717
Original Research
Schattauer GmbH

Effects of an opioid receptor agonist and antagonist on cytokine-stimulated canine articular chondrocytes in three-dimensional culture

N. H. Priddy II
1   Department of Veterinary Medicine and Surgery, Columbia, MO, USA
,
J. L. Cook
2   The Comparative Orthopaedic Laboratory, University of Missouri-Columbia, Columbia, MO, USA
,
J. R. Dodam
1   Department of Veterinary Medicine and Surgery, Columbia, MO, USA
,
J. M. Kreeger
2   The Comparative Orthopaedic Laboratory, University of Missouri-Columbia, Columbia, MO, USA
,
J. L. Tomlinson
2   The Comparative Orthopaedic Laboratory, University of Missouri-Columbia, Columbia, MO, USA
,
K. Kuroki
2   The Comparative Orthopaedic Laboratory, University of Missouri-Columbia, Columbia, MO, USA
› Author AffiliationsSupported by a grant from the University of Missouri-Columbia College of Veterinary Medicine Committee on Research.
Further Information

Publication History

Received 16 April 2001

Accepted 04 September 2001

Publication Date:
07 February 2018 (online)

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Summary

The objective of this study was to evaluate the effects of [D-Ala2, Nme-Phe4, Gly5-ol] enkephalin (DAMGO), a μ-opioid receptor agonist, and β-funaltrexamine (β-FNA), a μ-opioid receptor antagonist, on the biosynthetic capabilities of canine chondrocytes cultured in the presence of interleukin-1 β (IL-1 β). Articular chondrocytes were harvested from the humeral heads of three adult dogs and cultured in a three-dimensional (3-D) gel medium made from low-melting agarose and cell culture medium. Chondrocytes in 3-D culture were exposed to IL-1 β (0 or 20 ng/ml), DAMGO (0,0.1,1.0, or 10 μM), and β-FNA (0 or 10 μM) by addition to the liquid media in all possible combinations. On days five and 15 of 3-D culture, liquid medium samples were harvested for subsequent analysis of glycosaminogly- can (GAG), prostaglandin E2 (PGE2) and matrix metalloprotease-3 (MMP-3) content. On the same days, gel plugs were also harvested and evaluated for GAG content.

Incubation with IL-1 β decreased the amount of GAG in the gel plugs and caused an increase in PGE2 production on days five and 15 of 3-D culture. Treatment with DAMGO or β-FNA did not significantly modulate PGE2 production, MMP-3 production, GAG loss to the medium or GAG content of the gel plugs on either day five or 15 of 3-D culture in the presence or absence of IL-1 β. We concluded that DAMGO and β-FNA had neither protective nor detrimental effects on the biosynthetic capabilities of chondrocytes in the presence or absence of IL-1 β.

Keywords

Cartilage - interleukin-1 - prostaglandin E2 - matrix metalloprotease-3 (MMP-3)
 

  • References

  • 1 Stein C. Peripheral mechanisms of opioid analgesia. Anesth Analg 1993; 76: 182-91.
    PubMedSearch in Google Scholar
  • 2 Stein C, Hassan AH, Lehrberger K. et al. Local analgesic effect of endogenous opioid peptides. Lancet 1993; 342: 321-4.
    CrossrefPubMedSearch in Google Scholar
  • 3 Lawrence AJ, Joshi GP, Michalkiewicz A. et al. Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue. Eur J Clin Pharmacol 1992; 43: 351-5.
    CrossrefPubMedSearch in Google Scholar
  • 4 Nagasaka H, Awad H, Yaksh TL. Peripheral and spinal actions of opioids in the blockade of the autonomic response evoked by compression of the inflamed knee joint. Anesthesiology 1996; 85: 808-16.
    CrossrefPubMedSearch in Google Scholar
  • 5 Schäfer M, Imai Y, Uhl GR. et al. Inflammation enhances peripheral mu-opioid receptor- mediated analgesia, but not mu-opioid receptor transcription in dorsal root ganglia. Eur J Pharmacol 1995; 279: 165-9.
    CrossrefPubMedSearch in Google Scholar
  • 6 Likar R, Schäfer M, Paulak F. et al. Intraarticular morphine analgesia in chronic pain patients with osteoarthritis. Anesth Analg 1997; 84: 1313-7.
    CrossrefPubMedSearch in Google Scholar
  • 7 Stein C, Millan MJ, Shippenberg TS. et al. Peripheral opioid receptors mediating antinociception in inflammation. Evidence for invol-vement of mu, delta and kappa receptors. J Pharmacol ExpTher 1989; 248: 1269-75.
    PubMedSearch in Google Scholar
  • 8 Castaño MT, Freire-Garabal M, Giraldez M. et al. Autoradiographic evidence of 1251-beta- endorphin binding sites in the articular cartilage of the rat. Life Sci 1991; 49: 103-5.
    PubMedSearch in Google Scholar
  • 9 Freire-Garabal M, Castano MT, Belmoñte A. et al. Autoradiographic evidence of opioid binding sites in rat growth plate chondrocytes. Neuroendocrinology 1992; 55: 357-9.
    CrossrefPubMedSearch in Google Scholar
  • 10 Anderson CC, Cook JL, Kreeger JM. et al. In vitro effects of glucosamine and acetylsalicylate on canine chondrocytes in three-dimensional culture. Am J Vet Res 1999; 60: 1546-51.
    PubMedSearch in Google Scholar
  • 11 Cook JL, Anderson CC, Kreeger JM. et al. Effects of human recombinant Interleukin-IB on canine articular chondrocytes in threedimensional culture. Am J Vet Res 2000; 61: 766-70.
    CrossrefPubMedSearch in Google Scholar
  • 12 Cook JL, Kreeger JM, Payne JT. et al. Threedimensional culture of canine articular chondrocytes on multiple transplantable substrates. Am J Vet Res 1997; 58: 419-24.
    PubMedSearch in Google Scholar
  • 13 Verschure PJ, Van Noorden CJ. The effects of interleukin-1 on articular cartilage destruction as observed in arthritic diseases, and its therapeutic control. Clin Exp Rheumatol 1990; 08: 303-13.
    PubMedSearch in Google Scholar
  • 14 Hubbard JR, Steinberg JJ, Bednar MS. et al. Effect of purified human interleukin-1 on cartilage degradation. J Orthop Res 1988; 06: 180-7.
    CrossrefPubMedSearch in Google Scholar
  • 15 Pujol JP, Loyau G. Interleukin-1 and osteoarthritis. Life Sci 1987; 41: 1187-98.
    CrossrefPubMedSearch in Google Scholar
  • 16 Martel-Pelletier J, Alaaeddine N, Pelletier JP. Cytokines and their role in the pathophysiology of osteoarthritis. Front Biosci 1999; 04: D694-D703.
    CrossrefPubMedSearch in Google Scholar
  • 17 Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 1986; 883: 173-7.
    CrossrefPubMedSearch in Google Scholar
  • 18 Connor M, Christie MD. Opioid receptor signalling mechanisms. Clin Exp Pharmacol Physiol 1999; 26: 493-9.
    CrossrefPubMedSearch in Google Scholar
  • 19 Linder ME, Gilman AG. G proteins. Sci Am 1992; 267: 56-5.
    CrossrefPubMedSearch in Google Scholar
  • 20 Saklatvala J, Bird TA, Kaur P. et al. IL-1 signal transduction: evidence of activation of G protein and protein kinase. Prog Clin Biol Res 1990; 349: 285-95.
    PubMedSearch in Google Scholar
  • 21 Bankers-Fulbright JL, Kalli KR, McKean DJ. Interleukin-1 signal transduction. Life Sci 1996; 59: 61-83.
    CrossrefPubMedSearch in Google Scholar
  • 22 O’Neill LA. Interleukin I receptors and signal transduction. Biochem Soc Trans 1996; 24: 207-11.
    CrossrefPubMedSearch in Google Scholar
  • 23 Ahmed MS, Llanos QJ, Dinarello CA. et al. Interleukin 1 reduces opioid binding in guinea pig brain. Peptides 1985; 06: 1149-54.
    CrossrefPubMedSearch in Google Scholar
  • 24 Chang SL, Moldow RL, House SD. et al. Morphine affects the brain-immune axis by modulating an interleukin-1 beta dependent pathway. Adv Exp Med Biol 1996; 402: 35-42.
    PubMedSearch in Google Scholar
  • 25 Pool CW, Buijs RM, Swaab DF. et al. On the way to specific immunocytochemical localization. In: Cuello AC. ed. Immunohistochemistry. Chichester: Wiley & Sons; 1983: 1-46.
    Search in Google Scholar
  • 26 Madden JJ, Whaley WL, Ketelsen D. Opiate binding sites in the cellular immune system: expression and regulation. J Neuroimmunol 1998; 83: 57-62.
    CrossrefPubMedSearch in Google Scholar
  • 27 Maher CE, Selley DE, Childers SR. Relationship of mu opioid receptor binding to activation of G-proteins in specific rat brain regions. Biochem Pharmacol 2000; 59: 1395-401.
    CrossrefPubMedSearch in Google Scholar
  • 28 Rothman RB, Bykov V, Mahboubi A. et al. Interaction of beta-funaltrexamine with [3H] cycloFOXY binding in rat brain: further evidence that beta-FNA alkylates the opioid receptor complex. Synapse 1991; 08: 86-99.
    CrossrefPubMedSearch in Google Scholar
  • 29 Thurmon JC, Tranquilli WJ, Benson GJ. Preanesthetics and Anesthetic Adjuncts. In: Thurmon JC, Tranquilli WJ, Benson GJ. eds. Lumb & Jones’ Veterinary Anesthesia. 3 Ed. Baltimore: Lea & Febiger; 1996: 183-209.
    Search in Google Scholar
  • 30 Dalsgaard J, Felsby S, Juelsgaard P. et al. Low- dose intra-articular morphine analgesia in day case knee arthroscopy: a randomized doubleblinded prospective study. Pain 1994; 56: 151-4.
    CrossrefPubMedSearch in Google Scholar
  • 31 Bland JH, Cooper SM. Osteoarthritis: a review of the cell biology involved and evidence for reversibility. Management rationally related to known genesis and pathophysiology. Semin Arthritis Rheum 1984; 14: 106-33.
    CrossrefPubMedSearch in Google Scholar
  • 32 Pujol JP, Galera P, Redini F. et al. Role of cytokines in osteoarthritis: comparative effects of interleukin 1 and transforming growth factor- beta on cultured rabbit articular chondrocytes. J Rheumatol Suppl 1991; 27: 76-9.
    PubMedSearch in Google Scholar
  • 33 Tiku K, Thakker-Varia S, Ramachandrula A. et al. Articular chondrocytes secrete IL-1, express membrane IL-1, and have IL-1 inhibitory activity. Cell Immunol 1992; 140: 1-20.
    CrossrefPubMedSearch in Google Scholar
  • 34 Kalso E, Tramèr MR, Carroll D. et al. Pain relief from intra-articular morphine after knee surgery: a qualitative systematic review. Pain 1997; 71: 127-34.
    CrossrefPubMedSearch in Google Scholar
  • 35 Walker JS, Howlett CR, Nayanar V. Antiinflammatory effects of kappa-opioids in adjuvant arthritis. Life Sci 1995; 57: 371-8.
    CrossrefPubMedSearch in Google Scholar
  • 36 Wilson JL, Nayanar V, Walker JS. The site of anti-arthritic action of the kappa-opioid, U-50, 488H, in adjuvant arthritis: importance of local administration. Br J Pharmacol 1996; 118: 1754-60.
    CrossrefPubMedSearch in Google Scholar
  • 37 Rapaka RS, Porreca F. Development of delta opioid peptides as nonaddicting analgesics. Pharm Res 1991; 08: 1-8.
    CrossrefPubMedSearch in Google Scholar
  • 38 Malatynska E, Wang Y, Knapp RJ. et al. Human delta opioid receptor: functional studies on stably transfected Chinese hamster ovary cells after acute and chronic treatment with the selective nonpeptidic agonist SNC-80. J Pharmacol ExpTher 1996; 278: 1083-9.
    PubMedSearch in Google Scholar