Osteopontin and Wound Healing in Bone

Abstract

Bone wound healing after surgical drilling/cutting initially involves a typical inflammatory response with a leukocyte-rich cell infiltrate whose professional phagocytes (neutrophils and macrophages) clear the wound site of various bacterial (if present), particulate, and insoluble components arising from the original wounding event. As part of this process, in a surgical model of bone repair in rats, osteopontin (OPN) secreted by macrophages – with its known mineral-binding properties arising from abundant calcium-binding phosphorylations and overall net negative charge – binds to the newly exposed mineralized surfaces of particulate bone debris and the osseous wound margins created by the drilling, as shown by high-resolution immunogold labeling and transmission electron microscopy. For bone debris powder, OPN serves as an opsonin for clearance by macrophage phagocytosis, as demonstrated in vitro by phagocytosis assays using cultured J774.A1 murine macrophages and OPN-coated microbeads. Macrophage-secreted OPN binding to the bone wound margins contributes to cement line (plane) formation with subsequent OPN additions to the cement line coming from osteoblast lineage cells arriving at this site to effect bone repair upon further osteoblast differentiation, and extracellular matrix deposition and mineralization. Such interfacial OPN is thought to contribute to the cell adhesion, cell signaling, and matrix mineralization events required to effectively integrate the new bone into the preexisting bone at the margins of the drill site.

Enhanced osteogenic potential of mesenchymal stem cells from cortical bone: a comparative analysis

“…At a molecular level, our data support these observations showing a marked upregulation in Alp, Runx2, and Spp1 expression. Specifically, Alp and Runx2 are considered to play a critical role in the regulation of osteoblastogenesis, whereas Bglap and Spp1 are associated with a more mature differentiation [61][62][63]. In our study, although the expression of Bglap was similar between BM-MSCs and CBF-MSCs, CBF-MSCs were found to express higher levels of SSP1, confirming the more mature osteoblastogenesis even compared with BM-MSCs [17].…”

Effects of calcium ions on titanium surfaces for bone regeneration

“…First, the calcium ions rapidly released to the implant microenvironment promote clot formation and stabilization, platelet adhesion and activation and thereby growth factor release and/or storage within the clot [6] Second, the surface is presented to the body as a calcium source, a biochemical gradient for calciumbinding acidic proteins and osteogenic cells. [37][38][39] …”

A new strategy to enhance artificial ligament graft osseointegration in the bone tunnel using hydroxypropylcellulose

“…Some studies have shown that the presence of several important proteins and growth factors surrounding the graft, such as BMP-2, BMP-7 and osteopontin, could favour osteogenesis [23,[29][30][31][32]. Hashimoto et al [23] injected recombinant human BMP-2 (rhBMP-2) into the flexor digitorum communis tendon in the rabbit hind limb.…”

“…It is involved in a number of physiologic and pathologic events, including angiogenesis and wound healing [31]. McKee et al [32] found that during bone wound healing after surgical drilling and other forms of surgical cutting, the observed secretion of OPN by both macrophages and osteoblastlineage cells, together with the localization of osteopontin to exposed mineral surfaces, suggests that osteopontin plays important roles in (i) the clearance of bone debris (powder) by macrophage phagocytosis after osteopontin opsonization and (ii) the formation of a cement line (plane) at the margins of the wound that integrates the new repaired bone with the existing drilled bone. In our study, at week four after surgery, the mRNA expression level of osteopontin in the HPC group was higher than that in the control group.…”