Rheumatology International

, Volume 33, Issue 5, pp 1201–1206 | Cite as

The impact of chemical synovectomy with sodium morrhuate on human chondrocytes and cartilage in vitro

  • S. WinklerEmail author
  • S. Grässel
  • C. Baier
  • S. Anders
  • P. Lechler
  • J. Grifka
  • J. Schaumburger
Original Article


The vessel sclerosing property of sodium morrhuate is useful in treatment of recurrent joint effusions particularly in cases of knee joint effusions. It also can be employed as an addition to surgical synovectomy. Little is known about the effects of this drug on cartilage. This study was designed to investigate the cytotoxic impact of sodium morrhuate on human chondrocytes and cartilage tissue in vitro. Primary chondrocytes from 13 patients were isolated and cultivated in three-dimensional alginate cultures. Furthermore, femoral cartilage explants of 10 patients were cultivated in vitro. Both chondrocytes and cartilage explants were exposed to mixture of sodium morrhuate and mepivacaine in different concentrations simulating chemical synovectomy. After 48 h, cell proliferation, viability, and cytotoxicity were measured. The cartilage specimens were analyzed for apoptosis by immunohistochemistry. Up to a dilution of 1:600, cells were found to be 100 % viable with a proliferation rate of 74 % compared to controls. From 1:400 onwards, a significant increase in LDH release was measured which reached at dilution of 1:200 74 % of high control, whereas histological examination showed no proof of apoptosis or necrosis in cartilage tissue. The results of this in vitro study demonstrate that the cytotoxic effects of sodium morrhuate on human chondrocytes, which lack their original extracellular matrix, manifest between dilutions of 1:500 and 1:400 and increase with higher concentrations of the drug. This effect was not found for cartilage explants, though.


Sodium morrhuate Cartilage Chondrocytes Chemical synovectomy Cytotoxic effects 


Conflict of interest

There are no conflicts of interest.


  1. 1.
    Jahangier ZN, Jacobs JW, van Isselt JW, Bijlsma JW (1997) Persistent synovitis treated with radiation synovectomy using yttrium-90: a retrospective evaluation of 83 procedures for 45 patients. Br J Rheumatol 36(8):861–869PubMedCrossRefGoogle Scholar
  2. 2.
    Schneider P, Farahati J, Reiners C (2005) Radiosynovectomy in rheumatology, orthopedics, and hemophilia. J Nucl Med 46(Suppl 1):48S–54SPubMedGoogle Scholar
  3. 3.
    Sojan S, Bartholomeusz D (2005) Cutaneous radiation necrosis as a complication of yttrium-90 synovectomy. Hell J Nucl Med 8(1):58–59PubMedGoogle Scholar
  4. 4.
    Oztürk H, Oztemür Z, Bulut O (2008) Treatment of skin necrosis after radiation synovectomy with yttrium-90: a case report. Rheumatol Int 28(10):1067–1068PubMedCrossRefGoogle Scholar
  5. 5.
    Reis G, Swenson A (1951) Intra-articular injections of osmic acid in painful joint affections. Acta Med, Scand 259Google Scholar
  6. 6.
    Mohr W, Mohing W, Hersener J (1977) Morphological changes in the articular capsule tissue after preliminary synoviorthesis. Z Rheumatol 36(9–10):316–331PubMedGoogle Scholar
  7. 7.
    Bessant R, Steuer A, Rigby S, Gumpel M (2003) Osmic acid revisited: factors that predict a favourable response. Rheumatology (Oxford) 42(9):1036–1043CrossRefGoogle Scholar
  8. 8.
    Niculescu D, Tomescu E, Ionescu C, Cotutiu C, Hrisanidi S, Negoescu M, Cindea G, Stoia I (1976) Ultrastructural changes in cartilage after intra-articular administration of osmium tetroxide and the sodium salts of fish oil fatty acids (Varicocid). Scand J Rheumatol 5(3):133–140PubMedCrossRefGoogle Scholar
  9. 9.
    Kawasaki S, Henderson JM, Riepe SP, Brooks WS, Hertzler G (1992) Endoscopic variceal sclerosis does not increase the risk of portal venous thrombosis. Gastroenterology 102(1):206–215PubMedGoogle Scholar
  10. 10.
    Kitano S, Wada H, Yamaga H, Hashizume M, Koyanagi N, Iwanaga T, Iso Y, Sugimachi K (1991) Comparative effects of 5 % ethanolamine oleate versus 5 % sodium morrhuate for sclerotherapy of oesophageal varices. J Gastroenterol Hepatol 6(5):476–480PubMedCrossRefGoogle Scholar
  11. 11.
    Niculescu D, Stancuilescu P, Negoescu M, Ionescu I, Stoia I (1970) Chemical synovectomy using sodium salts of fatty acids. Z Rheumaforsch 29(1):27–35PubMedGoogle Scholar
  12. 12.
    Kästner P, Wessel G (1977) Chemical synovectomy with Varicocid in rheumatoid arthritis-further results. Scand J Rheumatol 6(1):28–32PubMedGoogle Scholar
  13. 13.
    Menninger H, Reinhardt S, Söndgen W (1994) Intra-articular treatment of rheumatoid knee-joint effusion with triamcinolone hexacetonide versus sodium morrhuate. A prospective study. Scand J Rheumatol 23(5):249–254PubMedCrossRefGoogle Scholar
  14. 14.
    Zacher J, Hagen H, Herr G (1992) Effects of sodium morrhuate (Varicocid) on the monolayer cell culture of human chondrocytes. Akt Rheumatol 17:178–186CrossRefGoogle Scholar
  15. 15.
    Näkel G, Soukup P, Schramm G (1980) Histological, histochemical and autoradiographical studies on the effect of Varicocid on rabbit joints. Beitr Orthop Traumatol 27(6):301–307PubMedGoogle Scholar
  16. 16.
    Zacher J, Hohenadel J, Herr G (1991) The Influence of synoviorthetic substances of the sodium morrhuate type on the monolayer cell culture of synovial fibroblasts. Akt Rheumatol 16:217–222CrossRefGoogle Scholar
  17. 17.
    Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A (2000) Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 374:212–234PubMedCrossRefGoogle Scholar
  18. 18.
    Häuselmann HJ, Aydelotte MB, Schumacher BL, Kuettner KE, Gitelis SH, Thonar EJ (1992) Synthesis and turnover of proteoglycans by human and bovine adult articular chondrocytes cultured in alginate beads. Matrix 12(2):116–129PubMedCrossRefGoogle Scholar
  19. 19.
    Häuselmann HJ, Fernandes RJ, Mok SS, Schmid TM, Block JA, Aydelotte MB, Kuettner KE, Thonar EJ (1994) Phenotypic stability of bovine articular chondrocytes after long-term culture in alginate beads. J Cell Sci 107(Pt 1):17–27PubMedGoogle Scholar
  20. 20.
    Grässel S, Rickert M, Opolka A, Bosserhoff A, Angele P, Grifka J, Anders S (2010) Coculture between periosteal explants and articular chondrocytes induces expression of TGF-beta1 and collagen I. Rheumatology (Oxford) 49(2):218–230CrossRefGoogle Scholar
  21. 21.
    Budihardjo I, Oliver H, Lutter M, Luo X, Wang X (1999) Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15:269–290PubMedCrossRefGoogle Scholar
  22. 22.
    Dreier R, Opolka A, Grifka J, Bruckner P, Grässel S (2008) Collagen IX-deficiency seriously compromises growth cartilage development in mice. Matrix Biol 27(4):319–329PubMedCrossRefGoogle Scholar
  23. 23.
    Thonar EJ, Buckwalter JA, Kuettner KE (1986) Maturation-related differences in the structure and composition of proteoglycans synthesized by chondrocytes from bovine articular cartilage. J Biol Chem 261(5):2467–2474PubMedGoogle Scholar
  24. 24.
    Deshmukh K, Kline WH (1976) Characterization of collagen and its precursors synthesized by rabbit-articular-cartilage cells in various culture systems. Eur J Biochem 69(1):117–123PubMedCrossRefGoogle Scholar
  25. 25.
    Dijkgraaf LC, de Bont LG, Boering G, Liem RS (1995) Normal cartilage structure, biochemistry, and metabolism: a review of the literature. J Oral Maxillofac Surg 53(8):924–929PubMedCrossRefGoogle Scholar
  26. 26.
    Brinkworth MH, Weinbauer GF, Schlatt S, Nieschlag E (1995) Identification of male germ cells undergoing apoptosis in adult rats. J Reprod Fertil 105(1):25–33PubMedCrossRefGoogle Scholar
  27. 27.
    Bartke A (1995) Apoptosis of male germ cells, a generalized or a cell type-specific phenomenon? Endocrinology 136(1):3–4PubMedCrossRefGoogle Scholar
  28. 28.
    Blaser J, Triebel S, Maasjosthusmann U, Romisch J, Krahl-Mateblowski U, Freudenberg W, Fricke R, Tschesche H (1996) Determination of metalloproteinases, plasminogen-activators and their inhibitors in the synovial fluids of patients with rheumatoid arthritis during chemical synoviorthesis. Clin Chim Acta 244(1):17–33PubMedCrossRefGoogle Scholar
  29. 29.
    John M, Oppermann J, John V (1987) The importance of arthrography and arthroscopy for the indication of synoviorthesis with Varicocid® in juvenile chronic arthritis—a therapeutic long-term study. Akt Rheumatol 12(3):231–233CrossRefGoogle Scholar
  30. 30.
    Schaumburger J, Trum S, Anders S, Beckmann J, Winkler S, Springorum H-R, Grifka J, Lechler P (2011) Chemical synovectomy with sodium morrhuate in the treatment of symptomatic recurrent knee joint effusion. Rheumatol Int. doi: 10.1007/s00296-011-2142-1 PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • S. Winkler
    • 1
    Email author
  • S. Grässel
    • 2
  • C. Baier
    • 1
  • S. Anders
    • 1
  • P. Lechler
    • 3
  • J. Grifka
    • 1
  • J. Schaumburger
    • 1
  1. 1.Department of Orthopaedic SurgeryUniversity of RegensburgBad AbbachGermany
  2. 2.Center for Medical Biotechnology, BioPark IUniversity of RegensburgRegensburgGermany
  3. 3.Department of Trauma, Hand and Reconstructive SurgeryUniversity of Giessen and Marburg, Location MarburgMarburgGermany

Personalised recommendations