title: Stimulation of pyrophosphate production in articular cartilage by a platelet-derived factor is independent of mitogenesis.
abstract: The disordered production of extracellular inorganic pyrophosphate (PPi) by cartilage contributes to calcium pyrophosphate dihydrate crystal formation and associated diseases. We have previously shown that a factor(s) derived from human platelets markedly stimulates the accumulation of PPi in the media of porcine articular cartilage in organ culture. This is the first known physiologic modifier of PPi production by cartilage. We report herein that platelet derived growth factor (PDGF) is not the platelet factor responsible for PPi stimulation and that the active factor is not mitogenic for chondrocytes. PDGF added to the media of articular cartilage explants in the presence of 0.5% (platelet-poor) plasma (PPP) produces 3.92 +/- 1.6 mumol/L PPi compared with 2.85 +/- 0.7 mumol/L PPi in cartilage exposed to PPP alone. The platelet extract (PE) and PDGF are mitogenic for adult articular chondrocytes in high-density monolayer cultures. Anti-PDGF antibodies block the mitogenic effects of PDGF and PE. The uptake of thymidine labeled with tritium is 157% of control in cells exposed to PE, PPP, and polyclonal goat immunoglobulin G (IgG); 114% of control in cells exposed to PE, PPP, and anti-PDGF antibody; 148% of control in cells treated with PDGF, PPP, and goat IgG; and 98% of control in cells treated with PDGF, PPP, and anti-PDGF antibody. However, anti-PDGF antibody has no effect on PPi accumulation. PPi levels are 17.22 +/- 1.6 mumol/L in media from cartilage treated with PPP, goat IgG, and PE and 17.62 +/- 2.2 mumol/L in cartilage exposed to PE, PPP, and anti-PDGF antibody. We have further characterized the platelet factor responsible for the stimulation of PPi by cartilage. It is not mitogenic for chondrocytes, and it is not PDGF.
authors.affiliation: Division of Rheumatology, Medical College of Wisconsin, Milwaukee.
authors.forename: A K
authors.initials: AK
authors.lastname: Rosenthal
authors.forename: H S
authors.initials: HS
authors.lastname: Cheung
authors.forename: L M
authors.initials: LM
authors.lastname: Ryan
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002457:Cell Extracts / Q000494:pharmacology*; D002478:Cells, Cultured; D011756:Diphosphates / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000494:pharmacology*; D013552:Swine; D013936:Thymidine / Q000378:metabolism; D014020:Tissue Extracts / Q000494:pharmacology*
chemical_list: D002457:Cell Extracts; D011756:Diphosphates; D007074:Immunoglobulin G; D010982:Platelet-Derived Growth Factor; D014020:Tissue Extracts; D013936:Thymidine