title: 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.
authors.affiliation: College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University , Baoding 071002, People's Republic of China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University , Baoding 071002, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University , Baoding 071002, People's Republic of China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University , Baoding 071002, People's Republic of China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.affiliation: College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University , Baoding 071002, People's Republic of China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University , Baoding 071002, People's Republic of China.
authors.forename: Cuimiao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University , Baoding 071002, People's Republic of China.
authors.forename: Jiadong
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University , Baoding 071002, People's Republic of China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University , Baoding 071002, People's Republic of China.
authors.forename: Weipei
authors.initials: W
authors.lastname: Feng
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, People's Republic of China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
authors.affiliation: College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University , Baoding 071002, People's Republic of China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University , Baoding 071002, People's Republic of China.
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University , Baoding 071002, People's Republic of China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University , Baoding 071002, People's Republic of China.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate; D001842:Bone and Bones; D002454:Cell Differentiation; D017886:Durapatite; D059630:Mesenchymal Stem Cells; D010012:Osteogenesis
chemical_list: D000255:Adenosine Triphosphate; D017886:Durapatite
keywords: ATP metabolism; cAMP/PKA pathway; defect-related hydroxyapatite; mesenchymal stem cell; osteogenic differentiation