Defect-Related Luminescent Hydroxyapatite-Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells Via an ATP-Induced cAMP/PKA Pathway

Abstract

Novel defect-related hydroxyapatite (DHAP), which combines the advantages of HAP and defect-related luminescence, has the potential application in tissue engineering and biomedical area, because of its excellent capability of monitoring the osteogenic differentiation and material biodegradation. Although the extracellular mechanism of DHAP minerals and PO4(3-) functioning in osteogenic differentiation has been widely studied, the intracellular molecular mechanism through which PO4(3-) mediates osteogenesis of bone mesenchymal stem cells (BMSCs) is not clear. We examined a previously unknown molecular mechanism through which PO4(3-) promoted osteogenesis of BMSCs with an emphasis on adenosine-triphosphate (ATP)-induced cAMP/PKA pathway. Our studies showed that DHAP could be uptaken into lysosome, in which PO4(3-) was released from DHAP, because of the acid environment of lysosome. The released PO4(3-) interacted with ADP to form ATP, and then degraded into adenosine, an ATP metabolite, which interacted with A2b adenosine receptor to activate the cAMP/PKA pathway, resulting in the high expression of osteogenesis-related genes, such as Runx2, BMP-2, and OCN. These findings first revealed the function of ATP-metabolism in bone physiological homeostasis, which may be developed to cure bone metabolic diseases.

Glycitin regulates osteoblasts through TGF-β or AKT signaling pathways in bone marrow stem cells

“…BMSCs are capable of osteogenic differentiation, which indicates the prospect of the clinical application for biotherapy based on BMSCs (19). Osteogenic differentiation of BMSCs, in vitro and in vivo, has been extensively studied (20,21). The results of the present study demonstrated that glycitin promotes cell proliferation, osteoblast induction, and activates Col I mRNA expression and ALP activity of BMSCs.…”

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property

“…activators, was detected before 50,51 and has a biomedical potential that extends beyond the scope of this study. 52,53 PL spectroscopy was used next to determine the type of defects present in ACP and HAp. The room temperature PL spectra are presented in Figs.…”

Oxidative stress-induced apoptosis of osteoblastic MC3T3-E1 cells by hydroxyapatite nanoparticles through lysosomal and mitochondrial pathways

“…9 We previously reported that defect-related luminescent hydroxyapatite could enhance osteogenic differentiation of BMSCs via an ATP-induced cAMP/PKA pathway. 10 Doostmohammadi et al conrmed that bone-derived HA were compatible with BMSCs and HAPs could be used for bone tissue engineering. 11 Sun et al used primary osteoblastic cells as model to detect the biocompatibility of different-sized HAPs, and found that larger HAPs had a good biocompatibility with primary osteoblastic cells while smaller-sized HAPs can both promote osteoclast activity and restrain osteoblasts activity, implying that size-dependent cytotoxicity of HAPs.…”