N A Athanasou

Macrophage-osteoclast differentiation and bone resorption in osteoarthrotic subchondral acetabular cysts.

A macrophage infiltrate is commonly found in enlarging subchondral cysts in osteoarthrosis (OA) and the surrounding bone. To determine whether osteoclast differentiation by these cells contributes to the increase in the number of osteoclasts and bone resorption that accompanies OA cyst enlargement, we isolated macrophages from the wall of OA cysts and co-cultured them with osteoblast-like UMR106 cells in the presence or absence of 1,25(OH) 2 D 3 and M-CSF. After 14 days of incubation, co-cultures of UMR106 cells and cyst-derived macrophages showed evidence of osteoclast differentiation by expression of TRAP, VNR and formation of numerous lacunar pits. We found that, unlike osteoclast precursors in monocyte and other tissue macrophage populations, the addition of M-CSF to medium is not required for osteoclast differentiation. Our findings suggest that macrophage-osteoclast differentiation is one means whereby the osteolysis associated with the enlargement of OA cysts could be effected.

Bisphosphonate Inhibition of bone resorption induced by particulate biomaterial-associated macrophages

Aseptic loosening of total joint replacements is associated with bone resorption. A heavy infiltrate of foreign body macrophages in response to biomaterial wear particles is commonly found in the fibrous membrane surrounding loose components. It has recently been shown that foreign body macrophages can differentiate into osteoclastic cells. To determine whether pharmacological inhibitors of bone resorption have a role to play in controlling the osteolysis of aseptic loosening, we analyzed the effect of a bisphosphonate, disodium ethane-1, 1-diphosphonate (EHDP) on this process. Murine monocytes and foreign body macrophages (derived from granulomas formed by subcutaneous implantation of particles of prosthetic biomaterials) were co-cultured with UMR106 osteoblast-like cells in the presence of 1,25 dihydroxyvitamin D3 for 14 days on glass coverslips and bone slices. EHDP significantly inhibited bone resorption in these co-cultures. There was little or no expression of the osteoclast-associated enzyme, tartrate-resistant acid phosphatase (TRAP) in EHDP-treated co-cultures. Addition of EHDP to monocyte-UMR106 co-cultures after the appearance of TRAP-positive cells did not abolish bone resorption, indicating that EHDP, in addition to its known inhibitory effect on osteoclast function, suppresses differentiation of osteoclast precursors. EHDP inhibition of the osteolysis induced by particulate biomaterial-associated macrophages shows that pharmacological inhibition of bone resorption might be used to control the osteolysis of aseptic loosening.