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Hyperleptinemia suppresses aggravation of arthritis of collagen-antibody-induced arthritis in mice

  • Original Article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

Leptin is an adipocytokine produced by adipocytes and controlling body weight. It is unclear whether leptin works as a proinflammatory or an anti-inflammatory cytokine. We investigated the effects of hyperleptinemia on leptin transgenic (LepTg) mice in terms of cartilage destruction, bone destruction, joint synovitis, and serum cytokine levels by using a mouse model of collagen-antibody-induced arthritis (CAIA).

Methods

CAIA was induced for female age-matched 6- to 8-week-old C57BL/6 J control mice and LepTg mice. Mice were injected intraperitoneally with 5 mg of a combination of monoclonal antibody specific for type II collagen on day 0 and 12.5 mg of lipopolysaccharide (LPS) on day 3. Clinical evaluation of arthritis was monitored for 14 days, and hind paws were examined clinically and histologically. Serum cytokine levels of interleukin (IL)-1β, IL-6, IL-10, and IL-17 and tumor necrosis factor alpha (TNF-α) were also analyzed on days 0 and 5. Moreover, THP-1 cells, which are human monocytic cell line derived from an acute monocytic leukemia patient, were cultured and differentiated into macrophages. The effects of leptin on messenger RNA (mRNA) expression of IL-6 were examined by real-time quantitative polymerase chain reaction (RT-PCR).

Results

Serum leptin concentrations were approximately ninefold higher in LepTg mice (62.0 ± 20.7 ng/ml) than in control mice (7.2 ± 0.5 ng/ml). Severity of clinical paw swelling, arthritis score, synovial hyperplasia, and cartilage damage were suppressed in LepTg mice with CAIA. Although serum cytokine levels of IL-1β, IL-17, and IL-10 and TNF-α showed no significant changes in two mice, serum levels of IL-6 in LepTg mice were suppressed at day 5. Moreover, in vitro study showed that IL-6 elevation following LPS exposure in THP-1 cells was suppressed with high leptin concentrations.

Conclusion

Our finding suggests that hyperleptinemia suppress IL-6 responses and progression of joint inflammation. Leptin may play an anti-inflammatory role under hyperleptinemia.

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Acknowledgments

The authors are grateful to Kanako Hata, Osaka City University Graduate School of Medicine, Japan, for providing us with technical assistance.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan

    Tadashi Okano, Masahiro Tada, Kenji Mamoto, Kentaro Inui & Hiroaki Nakamura

  2. Center for Senile Degenerative Disorders (CSDD), Osaka City University Medical School, 1-4-3 Asahi-machi Abeno-ku, Osaka, 545-8585, Japan

    Tatsuya Koike, Yuko Sugioka & Hiroyuki Okihana

  3. Search Institute for Bone and Arthritis Disease (SINBAD), Shirahama Health and Welfare Foundation, 1447 Shirahama-cho, Nishimuro-gun, Wakayama, 649-2211, Japan

    Tatsuya Koike

  4. Translational Research Center, Kyoto University Hospital, Kyoto University School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Ken Ebihara

  5. Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicne, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Kazuwa Nakao

Authors
  1. Tadashi Okano
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  2. Tatsuya Koike
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  3. Masahiro Tada
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  4. Yuko Sugioka
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  5. Kenji Mamoto
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  6. Kentaro Inui
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  7. Hiroyuki Okihana
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  8. Ken Ebihara
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  9. Kazuwa Nakao
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  10. Hiroaki Nakamura
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Corresponding author

Correspondence to Tatsuya Koike.

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Conflict of interest

Dr. Koike has received research grants and/or speaking fees from Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Eisai, Abbvie GK, Teijin Pharma, MSD K.K. and Ono Pharmaceutical. Dr. Inui has received research grants and/or speaking fees from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Abbvie GK, Eisai Co., Ltd., MSD K.K., Bristol-Myers K.K., Takeda Pharmaceutical Co., Ltd. and Janssen Pharmaceutical K.K. Dr. Nakamura has received research grants and/or speaking fees from Chugai Pharmaceutical, Astellas Pharma, Janssen Pharmaceutica, GlaxoSmithKline, Pfizer, Daiichi Sankyo and Ono Pharmaceutical. The other authors have no conflicts of interest to disclose.

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Okano, T., Koike, T., Tada, M. et al. Hyperleptinemia suppresses aggravation of arthritis of collagen-antibody-induced arthritis in mice. J Orthop Sci 20, 1106–1113 (2015). https://doi.org/10.1007/s00776-015-0768-7

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  • DOI: https://doi.org/10.1007/s00776-015-0768-7

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