Osteoclast-independent bone resorption by fibroblast-like cells

Abstract

Bone resorption by hyperplastic fibrous tissue is a characteristic feature of various disorders, and accumulating evidence suggests that transformed appearing, activated fibroblast-like cells play a key role in the pathogenesis of these conditions. One striking example is rheumatoid arthritis (RA), in which fibroblast-like synoviocytes constitute a considerable proportion of the hyperplastic synovium and are involved critically in the destruction of articular cartilage and bone [1]. Aseptic prosthesis loosening (APL), although apparently different at first sight, is also among these conditions and is characterized by the development of a synovial-like interface membrane (SLIM) between the prosthesis and the adjacent bone. Several studies have demonstrated similarities between the SLIM and the hyperplastic synovium in RA [2] and, intriguingly, there are a number of common features between fibroblast-like cells in RA and prosthesis loosening fibroblasts (PLFs) found at sites of bone resorption in APL. Recent data indicate that PLFs share some characteristic features of RA synovial fibroblasts, including anchorage-independent proliferation [3,4], escape of contact inhibition [5], APL = aseptic prosthesis loosening; FACS = fluorescent-activated cell sorter; FCS = foetal calf serum; ICSS = intracranially self-stimulated; PLF = prosthesis loosening fibroblast; RA = rheumatoid arthritis; SCID = severe combined immunodeficient; SLIM = synovial-like interface membrane; TNF = tumour necrosis factor. (Print ISSN 1478-6354; Online ISSN 1478-6362). This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. AbstractTo 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 p...

Fibroblast-like cells change gene expression of bone remodelling markers in transwell cultures

“…The synovial-like lining cells form the surface of the synovium-like interface, which consists mainly of periprosthetic fibroblast-like cells (PPFs). The PPFs have been shown to play an active role in periprosthetic osteolysis [ 7 ].…”

“…PPFs have been shown to play an active role in periprosthetic osteolysis [ 7 ], which is astonishing regarding their fibroblastic nature. PPFs are able to phagocytose many types of particles both in vivo and in vitro [ 4 ].…”

Osteolytic cancer cells induce vascular/axon guidance processes in the bone/bone marrow stroma

“…We observed cancer-associated fibroblasts (αSMA positive cells) in samples of human osteolytic bone metastasis. Fibroblast-like cells were previously described to mediate osteoclast-independent resorption, which could explain why these cells are present in osteolytic bone metastasis [ 47 ]. In human osteolytic bone metastasis cancer-associated fibroblasts and arteries are αSMA positive.…”

Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

“…Although the success rate of primary hip and knee arthroplasties exceeds 90% at 15 years [33], there is a significant need to extend the finite lifetime of current orthopaedic implants and improve implant function, particularly in challenging cases such as revisions, younger/more active patients, and conditions with compromised bone stock (e.g., osteoporosis) [33, 34]. It is important that the implants have strong adhesion with the host tissue as quickly as possible [35, 36] and begin healing process as delayed healing can result in fibrous tissue development [37, 38]. Stability of implants after surgery is very essential for successful osseointegration.…”