The role of ENPP1/PC-1 in osteoinduction by calcium phosphate ceramics

Abstract

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Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

“…Their success relies on their biocompatibility, bioactivity, osteoinductivity and osteoconductivity abilities [ 22 , 23 ]. The mechanism behind the osteoinductive capacity of CaP-based composites has been addressed by a proteomic analysis, which revealed the implication of plasma cell glycoprotein 1 (PC-1), encoded by the ectonucleotide pyrophosphatase/phosphodiesterase 1 gene ( ENPP1 ), which regulates the mineralization process by hydrolyzing adenosine triphosphate into adenosine monophosphate and pyrophosphate (PPi) [ 24 ]. In fact, only the cells in direct contact with CaP ceramics showed an increase in the expression of ENPP1 and PC-1 synthesis when compared to non-osteoinductive ceramics, together with other osteogenic markers (bone morphogenetic protein 2 (BMP-2) and Osteopontin), but without affecting the expression of alkaline phosphatase (ALP) [ 25 ].…”

“…Extracellular PPi levels are key in regulating the mineralization process; thus, PPi is hydrolyzed by ALP to yield inorganic phosphate, a precursor of bone mineral, but excess PPi inhibits bone mineralization and soft tissue calcification by binding to nascent HA crystals, preventing them from continuing to grow. The increased production of PPi by PC-1 in cells cultured in CaP-based scaffolds negatively regulates tissue mineralization, which draws attention to the modulation of ENPP1 expression as a regulatory response to CaP-induced human MSCs (hMSCs) differentiation to restrict further mineralization [ 24 ]. Moreover, the fact that EPNN1 /PC-1 over-expression occurs only in cells with direct contact with the ceramic, suggests that a chemically-driven process was occurring at the surface involving the exchange of calcium and phosphate ions between the medium and the material.…”

Improved Osteogenesis of Selective-Laser-Melted Titanium Alloy by Coating Strontium-Doped Phosphate With High-Efficiency Air-Plasma Treatment

“…Coatings containing calcium phosphate (CaP), the main component of natural bone tissue, can promote osteogenic differentiation of stem/progenitor cells. Various ceramics, nanoparticles, and scaffolds developed with CaP have been shown to enhance osteogenesis (de Jonge et al, 2010;Alghamdi et al, 2014;Zhou et al, 2017;Othman et al, 2019). The osteogenic nature of CaP is attributed to its ability to regulate both the extracellular Ca 2+ /PO 4 3− ions (Wu et al, 2003) and the adsorption/release of osteoinductive growth factors such as bone morphogenetic proteins (BMPs) (Begam et al, 2017).…”

Proliferation and Osteogenic Differentiation of hMSCs on Biomineralized Collagen

“…ALP and ENPP1 expression of cells cultured on the collagen membranes and biomineralized collagen were similar, with ENPP1 expression being slightly lower in the absence of mineral. ENPP1 expression has previously been shown to be upregulated on CaP ceramics with intrinsic osteoinductive potential (Othman et al, 2019). To our knowledge, this is, however, the first time that ENPP1 expression has been investigated on collagen and biomineralized collagen.…”