Molecular Medicine

, Volume 23, Issue 1, pp 57–69 | Cite as

α-1 Antitrypsin Inhibits RANKL-induced Osteoclast Formation and Functions

  • Mohammad Ahsanul Akbar
  • David Nardo
  • Mong-Jen Chen
  • Ahmed S. Elshikha
  • Rubina Ahamed
  • Eslam M. Elsayed
  • Claire Bigot
  • L. Shannon Holliday
  • Sihong Song
Research Article


Osteoporosis is a global public health problem affecting more than 200 million people worldwide. We previously showed that treatment with α-1 antitrypsin (AAT), a multifunctional protein with antiinflammatory properties, mitigated bone loss in an ovariectomized mouse model. However, the underlying mechanisms of the protective effect of AAT on bone tissue are largely unknown. In this study, we investigated the effect of AAT on osteoclast formation and function in vitro. Our results showed that AAT dose-dependently inhibited the formation of receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclasts derived from mouse bone marrow macrophage/monocyte (BMM) lineage cells and the RAW 264.7 murine macrophage cell line. To elucidate the possible mechanisms underlying this inhibition, we tested the effect of AAT on the gene expression of cell surface molecules, transcription factors and cytokines associated with osteoclast formation. We showed that AAT inhibited macrophage colony-stimulating factor (M-CSF)-induced cell surface RANK expression in osteoclast precursor cells. In addition, AAT inhibited RANKL-induced TNF-α production, cell surface CD9 expression and dendritic cell-specific transmembrane protein (DC-STAMP) gene expression. Importantly, AAT treatment significantly inhibited osteoclast-associated mineral resorption. Together, these results uncover new mechanisms for the protective effects of AAT and strongly support the notion that AAT has therapeutic potential for the treatment of osteoporosis.



EME is a visiting scholar from Zagazig University and is supported by a scholarship from the Egyptian government. We thank Dr. Jay Cao (US Department of Agriculture, Agriculture Research Service’s Grand Forks Human Nutrition Research Center) for his assistance with part of the gene expression studies and suggestions regarding induction of osteoclast formation.

This work was supported by a grant from the University of Florida.

Supplementary material

10020_2017_2301057_MOESM1_ESM.pdf (1.9 mb)
Supplementary material, approximately 1.88 MB.


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Authors and Affiliations

  • Mohammad Ahsanul Akbar
    • 1
  • David Nardo
    • 1
  • Mong-Jen Chen
    • 1
  • Ahmed S. Elshikha
    • 1
  • Rubina Ahamed
    • 1
  • Eslam M. Elsayed
    • 1
    • 4
  • Claire Bigot
    • 1
  • L. Shannon Holliday
    • 2
    • 3
  • Sihong Song
    • 1
    • 5
  1. 1.Department of Pharmaceutics, College of PharmacyUniversity of FloridaGainesvilleUSA
  2. 2.Department of Orthodontics, College of DentistryUniversity of FloridaGainesvilleUSA
  3. 3.Department of Anatomy and Cell Biology, College of MedicineUniversity of FloridaGainesvilleUSA
  4. 4.Department of Microbiology and Immunology, Faculty of PharmacyZagazig UniversityCairoEgypt
  5. 5.GainesvilleUSA

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