title: ATP promotes extracellular matrix biosynthesis of intervertebral disc cells.
abstract: We have recently found a high accumulation of extracellular adenosine triphosphate (ATP) in the center of healthy porcine intervertebral discs (IVD). Since ATP is a powerful extracellular signaling molecule, extracellular ATP accumulation might regulate biological activities in the IVD. The objective of this study was therefore to investigate the effects of extracellular ATP on the extracellular matrix (ECM) biosynthesis of porcine IVD cells isolated from two distinct anatomical regions: the annulus fibrosus (AF) and nucleus pulposus (NP). ATP treatment significantly promotes ECM deposition and corresponding gene expression (aggrecan and type II collagen) by both cell types in three-dimensional agarose culture. A significant increase in ECM accumulation has been found in AF cells at a lower ATP treatment level (20 μM) compared with NP cells (100 μM), indicating that AF cells are more sensitive to extracellular ATP than NP cells. NP cells also exhibit higher ECM accumulation and intracellular ATP than AF cells under control and treatment conditions, suggesting that NP cells are intrinsically more metabolically active. Moreover, ATP treatment also augments the intracellular ATP level in NP and AF cells. Our findings suggest that extracellular ATP not only promotes ECM biosynthesis via a molecular pathway, but also increases energy supply to fuel that process.
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Miami, P.O. Box 248294, Coral Gables, FL, 33124-0621, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gonzales
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Miami, P.O. Box 248294, Coral Gables, FL, 33124-0621, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurological Surgery, University of Miami, Miami, FL, 33136, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Levene
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Miami, P.O. Box 248294, Coral Gables, FL, 33124-0621, USA.|Geriatric Research, Education and Clinical Center, Miami Veterans Affairs Medical Center, Miami, FL, 33125, USA.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Cheung
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Miami, P.O. Box 248294, Coral Gables, FL, 33124-0621, USA. c.huang@miami.edu.
authors.forename: Chun-Yuh Charles
authors.initials: CC
authors.lastname: Huang
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D024043:Collagen Type II / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007403:Intervertebral Disc / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D034421:Sus scrofa
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D000255:Adenosine Triphosphate