Osteoclast-independent bone resorption by fibroblast-like cells

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.