Osteoclast Precursors: Cytokine-Stimulated Immunomodulators of Inflammatory Bone Disease

Curr Opin Rheumatol. 2006 Jul;18(4):427-32. doi: 10.1097/01.bor.0000231913.32364.32.

Abstract

Purpose of review: Proinflammatory cytokines produced in inflamed joints promote the generation and release from the bone marrow of osteoclast precursors (OCPs). These OCPs are recruited to inflamed joints where, in response to proinflammatory cytokines, they differentiate into osteoclasts and behave as immunomodulatory cells. We review the regulation of OCP formation and differentiation, and propose that they are not only sources of bone-resorbing osteoclasts, but also of immune cells that influence the progression of inflammatory bone diseases.

Recent findings: OCP numbers are increased in the blood of humans and animals with tumor necrosis factor (TNF)-mediated arthritis and they correlate with serum TNF levels, which can be lowered by anti-TNF therapy. TNF stimulates bone marrow OCP generation in part by increasing their expression of c-Fms. These precursors then leave the bone marrow and circulate in the blood stream. Receptor activator NF-kappaB ligand (RANKL) and TNF, which are elevated in inflamed joints, mediate OCP differentiation into osteoclasts and other cell types, including dendritic cells. They also stimulate OCPs to produce proinflammatory cytokines and chemokines. RANKL inhibition prevents joint inflammation in TNF-mediated arthritis.

Summary: OCPs are effector immunomodulatory cells in inflammatory bone diseases. They respond to and secrete cytokines, and are therefore targets for anti-inflammatory therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Bone Diseases / immunology*
  • Bone Diseases / physiopathology*
  • Cell Differentiation
  • Cytokines / immunology
  • Cytokines / physiology*
  • Humans
  • Immunologic Factors / immunology*
  • Models, Biological
  • Osteoclasts / cytology
  • Osteoclasts / immunology
  • Osteoclasts / physiology

Substances

  • Cytokines
  • Immunologic Factors