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Mitogen-activated protein kinases as therapeutic targets in osteoarthritis

Richard F Loeser1, Elizabeth A Erickson, David L Long

  • 1Department of Internal Medicine, Section of Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. rloeser@wfubmc.edu

Current Opinion in Rheumatology
|August 14, 2008
PubMed
Abstract

Insights

Mitogen-activated protein (MAP) kinase inhibition shows promise for slowing osteoarthritis progression and reducing pain. However, current safety concerns limit the use of general MAP kinase inhibitors in humans.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Rheumatology

Background:

  • Mitogen-activated protein (MAP) kinases are key intracellular signaling proteins.
  • They regulate pathways involved in joint tissue destruction in osteoarthritis.
  • MAP kinases are implicated in the production of inflammatory mediators and pain.

Purpose of the Study:

  • To review the therapeutic potential of MAP kinase inhibition in osteoarthritis.
  • To explore the role of MAP kinases in osteoarthritis pathogenesis.
  • To assess the current status of MAP kinase inhibitors for osteoarthritis treatment.

Main Methods:

  • Review of basic research studies, including cell culture and animal models.
  • Analysis of the role of MAP kinases in regulating inflammatory cytokines and metalloproteinases.
  • Evaluation of safety concerns associated with available MAP kinase inhibitors.

Main Results:

  • MAP kinases are central mediators of osteoarthritis, regulating proinflammatory cytokines and metalloproteinases.
  • Inhibition of MAP kinases may slow osteoarthritis progression, based on preclinical studies.
  • Clinical trials of MAP kinase inhibitors in human osteoarthritis are not yet reported.

Conclusions:

  • MAP kinase inhibition holds potential for slowing osteoarthritis progression and alleviating pain.
  • Safety concerns with current inhibitors restrict their use in humans.
  • Development of specific inhibitors with reduced toxicity is needed for structure-modifying osteoarthritis therapy.

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