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Updated: Jun 23, 2026

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
11:47

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders

Published on: June 8, 2014

Is there a role for NFAT inhibitors in the prevention of bone destruction?

Mark S McMahon1

  • 1Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. msmcmahon@att.net

HSS Journal : the Musculoskeletal Journal of Hospital for Special Surgery
|May 19, 2009
PubMed

Insights

Excessive bone destruction from conditions like osteoporosis may be treated by targeting the Nuclear Factor of activated T-cells (NFAT) pathway. NFAT inhibitors, such as Cyclosporin A and Tacrolimus, show promise for treating hyper-resorptive bone diseases.

Area of Science:

  • Bone biology and pathology
  • Immunology and drug discovery

Background:

  • Pathologic bone destruction underlies conditions including osteoporosis, rheumatoid arthritis, and metastatic disease.
  • Limited molecular targets in bone have hindered therapeutic development for bone-destructive diseases.
  • Nuclear Factor of activated T-cells (NFAT) is a key regulator of osteoclastogenesis, induced by RANKL.

Purpose of the Study:

  • To explore the therapeutic potential of targeting the NFAT/calcineurin pathway in osteoclastogenesis.
  • To evaluate existing immunosuppressive drugs as treatments for bone hyper-resorptive syndromes.

Main Methods:

  • Review of molecular mechanisms regulating osteoclast formation.
  • Analysis of the role of the NFAT/calcineurin pathway in osteoclastogenesis.
  • Assessment of NFAT inhibitors (Cyclosporin A, Tacrolimus) in the context of bone resorption.

Main Results:

  • NFAT is a critical mediator of osteoclast formation.
  • The NFAT/calcineurin pathway is a viable target for modulating bone resorption.
  • Immunosuppressive drugs targeting NFAT inhibit osteoclast formation.

Conclusions:

  • NFAT inhibitors represent a promising therapeutic strategy for bone hyper-resorptive syndromes.
  • Cyclosporin A and Tacrolimus warrant consideration for treating conditions characterized by excessive bone destruction.

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