Open Access Research article

Osteoclast-independent bone resorption by fibroblast-like cells

Thomas Pap12*, Anja Claus3, Susumu Ohtsu2, Klaus M Hummel3, Peter Schwartz4, Susanne Drynda1, Géza Pap5, Andreas Machner5, Bernhard Stein6, Michael George6, Renate E Gay2, Wolfram Neumann5, Steffen Gay2 and Wilhelm K Aicher7

Author Affiliations

1 Division of Experimental Rheumatology, Otto-von-Guericke University, Magdeburg, Germany

2 Center of Experimental Rheumatology, Department of Rheumatology, University Hospital, Zurich, Switzerland

3 Division of Nephrology and Rheumatology, Georg-August-University, Göttingen, Germany

4 Center of Anatomy, Georg-August-University, Göttingen, Germany

5 Clinic of Orthopedic Surgery, Otto-von-Guericke-University, Magdeburg, Germany

6 Institute for Applied Physics, Ludwig-Maximilians-University, Munich, Germany

7 Research Laboratory, Clinic of Orthopedic Surgery, Tuebingen, Germany

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Arthritis Res Ther 2003, 5:R163-R173  doi:10.1186/ar752

Published: 26 March 2003

Abstract

To date, mesenchymal cells have only been associated with bone resorption indirectly, and it has been hypothesized that the degradation of bone is associated exclusively with specific functions of osteoclasts. Here we show, in aseptic prosthesis loosening, that aggressive fibroblasts at the bone surface actively contribute to bone resorption and that this is independent of osteoclasts. In two separate models (a severe combined immunodeficient mouse coimplantation model and a dentin pit formation assay), these cells produce signs of bone resorption that are similar to those in early osteoclastic resorption. In an animal model of aseptic prosthesis loosening (i.e. intracranially self-stimulated rats), it is shown that these fibroblasts acquire their ability to degrade bone early on in their differentiation. Upon stimulation, such fibroblasts readily release acidic components that lower the pH of their pericellular milieu. Through the use of specific inhibitors, pericellular acidification is shown to involve the action of vacuolar type ATPases. Although fibroblasts, as mesenchymal derived cells, are thought to be incapable of resorbing bone, the present study provides the first evidence to challenge this widely held belief. It is demonstrated that fibroblast-like cells, under pathological conditions, may not only enhance but also actively contribute to bone resorption. These cells should therefore be considered novel therapeutic targets in the treatment of bone destructive disorders.

Keywords:
aseptic prosthesis loosening; bone resorption; dentin; fibroblasts; severe combined immunodeficient mouse