Fibroblasts from the inner granulation tissue of the pseudocapsule in hips at revision arthroplasty induce osteoclast differentiation, as do stromal cells

Abstract

Background: It has previously been shown that many osteoclast precursors are included in the granulation tissue within the pseudocapsule obtained at revision arthroplasty from hips with osteolysis. In vitro culture of only cells isolated from the granulation tissue has been previously shown to generate many mature osteoclasts. Objective: To investigate the presence or otherwise of supporting cells, similar to stromal cells, which differentiate osteoclasts within the granulation tissue. Methods: Cells isolated from the granulation tissue were cultured alone, and after four weeks fibroblast-like cells (granulation fibroblasts) remained. Rat non-adherent bone marrow cells (NA-BMCs) were co-cultured with the granulation fibroblasts with or without 1α,25(OH) 2 D 3 (10 −8 M) or heat treated ROS 17/2.8 cell conditioned medium (ht ROSCM), or both. Multinucleated cells (MNCs), which formed, were assessed by biochemical and functional characterisation of osteoclasts. Receptor activator of NFκB ligand (RANKL) was investigated by immunohistochemistry. Results: Co-culture of NA-BMCs and granulation fibroblasts caused the formation of tartrate resistant acid phosphatase (TRAP) positive MNCs, which had the calcitonin receptor (CTR), the Kat-1 antigen, which is specific to the surface of rat osteoclasts, and the ability to form pits in the presence of both 1α,25(OH) 2 D 3 and ht ROSCM or in the presence of just ht ROSCM. RANKL was detected in fibroblastlike cells in the granulation tissue. Conclusion: These data suggest that granulation fibroblasts support osteoclast differentiation, as do osteoblasts/stromal cells, and may play a part in aseptic loosening.

Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction

“…7 The presence of abundant mononuclear osteoclast precursors is also present in the synovial membrane of patients with rheumatoid arthritis. 8 Helper T-cell subsets are also shown to be involved in the incidence of periodontal disease, 9 which could contribute to severe bone destruction in the inflammatory sites.…”

Role of fibroblasts and fibroblast‐derived growth factors in periprosthetic angiogenesis

“…3,[5][6][7] Macrophages are the key players in this inexorable process, 3,[8][9][10] but other cell types, such as activated fibroblasts, [11][12][13][14][15] or osteoblasts with acquired dysfunction in type I collagen synthesis, 6,16 are significant contributors to the unbalanced bone remodeling leading to periprosthetic osteolysis and loosening of prosthetic components. Fibroblasts can also phagocytose particles both in vivo and in vitro, 15 produce and respond to a number of inflammatory mediators and growth factors, 12,14,15,[17][18][19][20] and importantly express RANKL in response to Ti phagocytosis, TNFa or IL-1b stimulation, at a level that seems to be sufficient to induce osteoclastogenesis. 14,15,21 In a previous study, we have isolated synovial tissues from normal, rheumatoid, and osteoarthritic joints, and compared their gene expression profiles and cytokine/chemokine expressions with those derived from IFM.…”

Inflammatory Periprosthetic Bone Loss

“…However, the relatively low numbers of T cells present near periprosthetic osteolysis make it unlikely that T cells are the major source of RANKL in periprosthetic osteolysis. Studies of periprosthetic membranes of osteolysis patients revealed that fibroblast are the major source of RANKL (Haynes et al, 2004;Sakai et al, 2002), with possible involvement of macrophages and giant cells (Haynes et al, 2004;Sakai et al, 2002). Expression and secretion of MMPs are also elevated in macrophages exposed to wear debris in vitro.…”