The importance of WNT pathways for bone metabolism and their regulation by implant topography

Abstract

Endosseous implants are important tools to replace missing teeth or damaged tissue segments. Their clinical success depends on their integration in bone and, thus, on the response of bone cells to material and surface characteristics. Recent evidence has shown that surface topography and chemistry affect WNT signalling, a pivotal pathway for the commitment of mesenchymal progenitors to the osteoblast lineage and for bone homeostasis. WNT signalling comprises several cascades that, acting through different effectors, modulate several aspects of cell behaviour. It has been shown that cells growing on rough titanium surfaces display a different expression profile for WNT factors, and that surface features can alter the response of bone cells to WNT factors. Although the underlying mechanisms to this regulation are still poorly understood, the present review reports intriguing evidence that that cell cytoskeletal signalling is involved in activating WNT signalling in cells growing on rough implant surfaces.

Osteoblasts preferentially adhere to peaks on micro-structured titanium

“…Ever since implant surfaces with different degrees of roughness were introduced into the clinical use, investigators realised that the way cells and tissue interacted with smooth or rough surfaces was profoundly different 2,17,25) . Tailored experiments have since proved that cells are indeed capable to translate geometric cues into intracellular signals that then can affect cell fate and activity 7,9,26,27) . More specifically micro-rough surfaces were demonstrated to enhance the expression of osteoblast-specific genes such as alkaline phosphatase, osteoprotegerin or osteocalcin 2,25,28,29) , thus attracting the attention of the scientific world as good candidates for endosseous devices because of their improved integration in bone 30) .…”

Structural and functional insights into sclerostin-glycosaminoglycan interactions in bone

“…Sclerostin is a secreted glycoprotein, which acts as an endogenous inhibitor of Wnt signaling by hindering Wnt ligands to bind to their co-receptor low-density lipoprotein receptor-related protein 5/6 (LRP5/6). Wnt target genes that are affected by sclerostin include key regulators of osteoblast, osteoclast and osteocyte differentiation and function such as alkaline phosphatase, osteoprotegerin (OPG), connexin-43, and cyclooxygenase 2 [1,2]. The essential role of sclerostin for bone biology is highlighted by the fact that humans with inherited sclerostin deficiency display a generalized increase of bone mass and strength, which confers protection against fractures [3].…”

Osteogenic differentiation and proliferation of bone marrow‐derived mesenchymal stromal cells on PDLLA + BMP‐2‐coated titanium alloy surfaces

“…In turn, it was described that extreme smoothened titanium surfaces in the subnano scale do not activate integrin receptors of murine hMSC sufficiently when compared to the nano and submicron group . In summary, hMSC on native titanium can be influenced by special surface features including roughness that activate integrin receptors resulting in WNT signaling enhanced osteogenic differentiation …”