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Bone corticalization requires local SOCS3 activity and is promoted by androgen action via interleukin-6

Author

Listed:
  • Dae-Chul Cho

    (St. Vincent’s Institute of Medical Research
    Kyungpook National University Hospital)

  • Holly J. Brennan

    (St. Vincent’s Institute of Medical Research
    University of Melbourne)

  • Rachelle W. Johnson

    (St. Vincent’s Institute of Medical Research
    Vanderbilt University)

  • Ingrid J. Poulton

    (St. Vincent’s Institute of Medical Research)

  • Jonathan H. Gooi

    (University of Melbourne)

  • Brett A. Tonkin

    (St. Vincent’s Institute of Medical Research)

  • Narelle E. McGregor

    (St. Vincent’s Institute of Medical Research)

  • Emma C. Walker

    (St. Vincent’s Institute of Medical Research)

  • David J. Handelsman

    (University of Sydney)

  • T. J. Martin

    (St. Vincent’s Institute of Medical Research
    University of Melbourne)

  • Natalie A. Sims

    (St. Vincent’s Institute of Medical Research
    University of Melbourne)

Abstract

Long bone strength is determined by its outer shell (cortical bone), which forms by coalescence of thin trabeculae at the metaphysis (corticalization), but the factors that control this process are unknown. Here we show that SOCS3-dependent cytokine expression regulates bone corticalization. Young male and female Dmp1Cre.Socs3 f/f mice, in which SOCS3 has been ablated in osteocytes, have high trabecular bone volume and poorly defined metaphyseal cortices. After puberty, male mice recover, but female corticalization is still impaired, leading to a lasting defect in bone strength. The phenotype depends on sex-steroid hormones: dihydrotestosterone treatment of gonadectomized female Dmp1Cre.Socs3 f/f mice restores normal cortical morphology, whereas in males, estradiol treatment, or IL-6 deletion, recapitulates the female phenotype. This suggests that androgen action promotes metaphyseal corticalization, at least in part, via IL-6 signaling.

Suggested Citation

  • Dae-Chul Cho & Holly J. Brennan & Rachelle W. Johnson & Ingrid J. Poulton & Jonathan H. Gooi & Brett A. Tonkin & Narelle E. McGregor & Emma C. Walker & David J. Handelsman & T. J. Martin & Natalie A. , 2017. "Bone corticalization requires local SOCS3 activity and is promoted by androgen action via interleukin-6," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00920-x
    DOI: 10.1038/s41467-017-00920-x
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    Cited by:

    1. Prachand Issarapu & Manisha Arumalla & Hannah R. Elliott & Suraj S. Nongmaithem & Alagu Sankareswaran & Modupeh Betts & Sara Sajjadi & Noah J. Kessler & Swati Bayyana & Sohail R. Mansuri & Maria Derak, 2023. "DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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