The influence of surface mineral and osteopontin on the formation and function of murine bone marrow-derived osteoclasts

Abstract

The phosphorylated glycoprotein osteopontin (OPN) is involved in the regulation of biomineralization under normal and pathological conditions. Its actions include inhibiting apatite crystal growth and promoting the formation and function of mineral resorbing cells, including osteoclasts (OCL). The purpose of this study was to develop stable apatitic mineral surfaces and determine their influence on OCL formation and mineral resorption from bone marrow macrophages derived from OPN wild-type (OPN +/+) and OPN deficient (OPN-/-) mice. We demonstrated that these mineral coatings were stable and supported bone marrow-derived macrophage differentiation to OCL under our culture conditions. Macrophages harvested from OPN-/-mice had a greater capacity to form OCL than macrophages from OPN+/+ mice when allowed to differentiate on tissue culture plastic. In contrast, when allowed to differentiate on a mineral surface, no difference in OCL formation was observed. Interestingly, OPN+/+ OCL were more efficient at mineral dissolution than OPN-/-OCL, and this difference was observed regardless of differentiating surface. Our results suggest that mineralized substrates as well as ability to synthesize OPN both control OCL function in our model system. The exact nature of these effects may be dependent on variables related to mineral substrate presentation.

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

“…These findings stress earlier studies on the impact of mineral substrates on osteoclastogenesis, which showed increased osteoclast formation of osteopontin-deficient cells when culture was performed on plastic that was no longer present when culture was performed on bone (40). However, F-actin staining demonstrated that S100A8-stimulated osteoclasts contained significantly more actin rings per cell.…”

Fibronectin inhibits osteoclastogenesis while enhancing osteoclast activity via nitric oxide and interleukin‐1β‐mediated signaling pathways

“…In contrast, Rajachar et al [2008] showed that OPN À / À bone marrow-derived macrophages formed more osteoclasts on TCP than OPN þ / þ macrophages, a finding consistent with previous in vitro and in vivo investigations of OPN null mice [Rittling et al, 1998;Chellaiah et al, 2003b]. Although we found no difference in osteoclast number on OPN compared to HA, all resorption parameters were elevated except for sealing zone formation.…”

“…Although we found no difference in osteoclast number on OPN compared to HA, all resorption parameters were elevated except for sealing zone formation. This increased resorptive capacity in the presence of OPN, with the exception of one study [Contractor et al, 2005], matches the rest of the literature demonstrating that OPN is required for proper bone resorption both in vivo and in vitro [Razzouk et al, 2002;Chellaiah et al, 2003b;Rajachar et al, 2008]. Taken together, these results highlight the important contribution of matrix proteins in modulating bone remodeling.…”

“…While OPN's stimulatory effect on osteoclasts has been shown extensively [Rittling et al, 1998;Razzouk et al, 2002;Chellaiah et al, 2003b;Contractor et al, 2005;Rajachar et al, 2008;Ek-Rylander and Andersson, 2010], studies on FN and VN have been limited to investigating mature osteoclast attachment [Flores et al, 1992;Abu-Amer et al, 1997;Hu et al, 2008]. Here we hypothesize that FN and VN, similar to OPN, have stimulatory effects on both osteoclast formation and resorption.…”

Increased serum osteopontin is a risk factor for osteoporosis in menopausal women

“…OPN works as an anchor to promote attachment of osteoclasts to bone for bone resorption. Osteoclasts deficient in OPN are hypomotile and exhibit decreased capacity for bone resorption, and bones lacking OPN are less readily remodeled [35][36][37]. The differentiation of cells of the monocytic lineage into mature osteoclasts is specifically induced by the tumor necrosis factor-related factor and receptor activator of NF-κB ligand (RANKL) [38].…”