Osteoinductivity of calcium phosphate mediated by connexin 43

Abstract

Recent reports have alluded to the osteoinductive properties of calcium phosphate, yet the cellular processes behind this are not well understood. To gain insight into the molecular mechanisms of this phenomenon, we have conducted a series of in vitro and in vivo experiments using a scaffoldless three dimensional (3D) dental pulp cell (DPC) construct as a physiologically relevant model. We demonstrate that amorphous calcium phosphate (ACP) alters cellular functions and 3D spatial tissue differentiation patterns by increasing local calcium concentration, which modulates connexin 43 (Cx43)-mediated gap junctions. These observations indicate a chemical mechanism for osteoinductivity of calcium phosphates. These results provide new insights for possible roles of mineral phases in bone formation and remodeling. This study also emphasizes the strong effect of scaffold materials on cellular functions and is expected to advance the design of future tissue engineering materials.

Bone morphogenetic protein Smads signaling in mesenchymal stem cells affected by osteoinductive calcium phosphate ceramics

“…Recently, researchers came up with theories that the materials could trigger secretion of factors rather than accumulation of factors leading to bone formation . Some researchers focused on the direct effect of materials on the multipotential cells which could eventually differentiate into osteocytes, such as adipose‐derived stem cells, dental pulp cells, C2C12 cells, and bone marrow MSCs . All these studies above make it more reasonable that the osteoinductive feature of materials might be due to its ability to directly induce the MSCs differentiation along osteoblastic linage.…”

Influence of surface microstructure and chemistry on osteoinduction and osteoclastogenesis by biphasic calcium phosphate discs

“…The biological relevance of surface reactivity and a precipitated layer of carbonate apatite is speculated to be either a direct physicochemical trigger for osteogenesis (i.e., the differentiation of bone forming osteoblasts from uncommitted precursors) through elevated local calcium and phosphate levels (Barradas et al, 2013;Beck et al, 2000;Syed-Picard et al, 2013), or a biomimetic template for bone deposition following osteoblast differentiation by another means (LeGeros, 2008). However, surface reactivity and carbonate apatite precipitation may only be a permissive factor in osteoinduction, not an osteogenic trigger.…”

Cell interactions between human progenitor-derived endothelial cells and human mesenchymal stem cells in a three-dimensional macroporous polysaccharide-based scaffold promote osteogenesis

“…At least two cell signaling pathways have been described that could explain the reciprocal activities on both cell types described above: (i) signals that are allowed to diffuse freely in the extracellular environment and interact with the target cells through specific receptors, and (ii) signals that freely diffuse from the cytoplasm of one cell to that of another via gap junctions, which directly link the cytoplasm of adjacent cells [33]. However, there is a lack of systemic studies evaluating the mode of cell communication in a 3-D scaffold, which could support bone tissue engineering Recently, the osteoinductivity of calcium phosphate as scaffolds, mediated by Connexin 43 (Cx43) has been demonstrated [34]. The authors showed that the scaffold had increased Cx43 expression and gap junction formation, which altered cell differentiation of dental pulp cells.…”