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Effects of testosterone, estrogen and progesterone on TNF-α mediated cellular damage in rat arthritic synovial fibroblasts

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Abstract

Sexual dimorphism is a well-established phenomenon in rheumatoid arthritis, with women exhibiting higher disease severity. Understanding the role of sex hormones using in vivo animal models is limited due to the systemic effects as well as the difficulty in exploring different dose combinations of the hormones simultaneously. However, cell culture systems pose ideal systems for exploring different combinations and concentrations of the hormones simultaneously. In this study, the procedure for isolation of arthritic fibroblasts was standardized using a combination of collagenase and trypsin based on maximal yield and viability after employing different enzymatic disaggregation procedures. The cultured synovial fibroblasts from arthritic rats did not differ significantly from normal rat fibroblasts in terms of proliferation or secretion of inflammatory mediators. Stimulation of fibroblasts with TNF-α was standardized and TNF-α stimulated rat arthritic synovial fibroblasts exhibited an ideal in vitro system for screening antiinflammatory molecules. The effects of physiological and pharmacological concentrations of testosterone, estrogen and progesterone were studied on TNF-α induced cellular damage in rat arthritic synovial fibroblasts. The results showed that estrogen and testosterone exerted antiinflammatory effects on rat arthritic synovial fibroblasts at physiological and pharmacological concentrations. However, there was no significant difference in the effects between physiological and pharmacological concentrations. Progesterone independently did not show any protective effects. In combination with physiological concentrations of estrogen, progesterone abrogated estrogen’s protective effect but it exhibited protection in combination with pharmacological concentrations of estrogen.

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Acknowledgments

The authors thank Dr. A.B. Mandal, Director, CLRI for his kind permission to publish this work. The award of CSIR fellowship to Dr. Kalaivani Ganesan and the CSIR Emeritus Scientist Project to Dr. R. Puvanakrishnan are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai, India

    Kalaivani Ganesan & Rengarajulu Puvanakrishnan

  2. Department of Veterinary Pathology, Madras Veterinary College, Vepery, Chennai, India

    Chidambaram Balachandran

  3. Centre for Animal Health Studies, TamilNadu Veterinary and Animal Sciences University, Madhavaram, Chennai, India

    Bhakthavatsalam Murali Manohar

Authors
  1. Kalaivani Ganesan
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  2. Chidambaram Balachandran
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  3. Bhakthavatsalam Murali Manohar
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  4. Rengarajulu Puvanakrishnan
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Correspondence to Rengarajulu Puvanakrishnan.

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Ganesan, K., Balachandran, C., Manohar, B.M. et al. Effects of testosterone, estrogen and progesterone on TNF-α mediated cellular damage in rat arthritic synovial fibroblasts. Rheumatol Int 32, 3181–3188 (2012). https://doi.org/10.1007/s00296-011-2146-x

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  • DOI: https://doi.org/10.1007/s00296-011-2146-x

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