title: Inorganic polyphosphate stimulates cartilage tissue formation.
abstract: Clinical utilization of tissue-engineered cartilage constructs has been limited by their inferior mechanical properties compared to native articular cartilage. A number of strategies have been investigated to increase the accumulation of major extracellular matrix components within in vitro-formed cartilage, including the administration of growth factors and mechanical stimulation. In this study, the anabolic effect of inorganic polyphosphates, a linear polymer of orthophosphate residues linked by phosphoanhydride bonds, was demonstrated in both chondrocyte cultures and native articular cartilage cultured ex vivo. Compared to untreated controls, polyphosphate treatment of three-dimensional primary chondrocyte cultures induced increased glycosaminoglycan and collagen accumulation in a concentration- and chain length-dependent manner. This effect was transient, because chondrocytes express exopolyphosphatases that hydrolyze polyphosphate. The anabolic effect of polyphosphates was accompanied by a lower rate of DNA increase within the chondrocyte cultures treated with inorganic polyphosphate. Inorganic polyphosphate enhances cartilage matrix accumulation and is a promising approach to improve the quality of tissue-engineered cartilage constructs.
authors.affiliation: CIHR BioEngineering of Skeletal Tissues Team, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: St-Pierre
authors.forename: Qishan
authors.initials: Q
authors.lastname: Wang
authors.forename: Shu Qiu
authors.initials: SQ
authors.lastname: Li
authors.forename: Robert M
authors.initials: RM
authors.lastname: Pilliar
authors.forename: Rita A
authors.initials: RA
authors.lastname: Kandel
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects* / Q000235:genetics; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D011122:Polyphosphates / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D023822:Tissue Engineering
chemical_list: D011122:Polyphosphates; D004247:DNA; D017766:Acid Anhydride Hydrolases; C022563:endopolyphosphatase