The role of cytokines in inflammatory bone loss

Abstract

Chronic inflammatory processes close to bone often lead to loss of bone in diseases such as rheumatoid arthritis, periodontitis, loosened joint prosthesis and tooth implants. This is mainly due to local formation of bone resorbing osteoclasts which degrade bone without any subsequent coupling to new bone formation. Crucial for osteoclastogenesis is stimulation of mononuclear osteoclast progenitors by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) which induces their differentiation along the osteoclastic lineage and the fusion to mature, multinucleated osteoclasts. M-CSF and RANKL are produced by osteoblasts/osteocytes and by synovial and periodontal fibroblasts and the expression is regulated by pro- and anti-inflammatory cytokines. These cytokines also regulate osteoclastic differentiation by direct effects on the progenitor cells. In the present overview, we introduce the basic concepts of osteoclast progenitor cell differentiation and summarize the current knowledge on cytokines stimulating and inhibiting osteoclastogenesis by direct and indirect mechanisms.

• Bone loss
• cytokines
• inflammation
• osteoclasts

Declaration of interests

Our own work discussed in this manuscript was supported by the Swedish Research Council for Medicine (proj. no 7525), the Swedish Rheumatism Association, the Royal 80 Year Fund of King Gustav V, Combine, the County Council of Västerbotten, ALF/TUA at Sahlgrenska University Hospital, the Medical Faculty, Umeå University, the Swedish Dental Society, Salus Ansvar, the Lundberg Foundation, and Fundação de Amparo à Pesquisa do Estado de São Paulo (Grants 2008/58958-7, 2008/07221-4).

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.