title: Artificial cartilage bio-matrix formed of hyaluronic acid and Mg2+-polyphosphate.
abstract: Here we show that inorganic polyphosphate (polyP), a polyanionic metabolic regulator consisting of multiple phosphate residues linked by energy-rich phosphoanhydride bonds, is present in the synovial fluid. In a biomimetic approach, to enhance cartilage synthesis and regeneration, we prepared amorphous polyP microparticles with Mg2+ as counterions. The particles were characterised by X-ray diffraction (XRD), energy-dispersive X-ray (EDX) and Fourier transformed infrared spectroscopic (FTIR) analyses. Similar particles were obtained after addition of Mg2+ ions to a solution containing hyaluronic acid, as a major component of the synovial fluid, and soluble Na-polyP. The viscous paste-like material formed, composed of globular microparticles with diameter of 400 nm, strongly promoted the adhesion of chondrocytes and caused a significant upregulation of the expression of the genes encoding collagen type 3A1, as a marker for chondrocyte differentiation, and SOX9, a transcription factor that regulates chondrocyte differentiation and proliferation. The expression level of the collagen type 3A1 gene was also enhanced by exposure of chondrocytes to synovial fluid that was found to contain polyP with a size of about 80 phosphate residues. This stimulatory effect was abolished after pre-incubation of the synovial fluid with the polyP degrading alkaline phosphatase. We propose a strategy for treatment of joint dysfunctions caused by osteoarthritis based on the application of amorphous Mg2+-polyP microparticles thatprevent calcium crystal formation in the synovial fluid using scavenging Ca2+ ions (Mg2+/Ca2+ exchange) and enhance chondrocyte function after binding of the Ca2+-polyP to hyaluronic acid at the cartilage surface.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Ackermann
authors.forename: E
authors.initials: E
authors.lastname: Tolba
authors.forename: M
authors.initials: M
authors.lastname: Neufurth
authors.forename: F
authors.initials: F
authors.lastname: Wurm
authors.forename: Q
authors.initials: Q
authors.lastname: Feng
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: H C
authors.initials: HC
authors.lastname: Schröder
authors.affiliation: University Medical Centre of the Johannes Gutenberg University Mainz, D-55128 Mainz, Germany.wmueller@uni-mainz.de.
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D002356:Cartilage / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D011122:Polyphosphates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission; D017550:Spectroscopy, Fourier Transform Infrared; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014961:X-Ray Diffraction
chemical_list: C439971:COL3A1 protein, human; D024061:Collagen Type III; D011122:Polyphosphates; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; D006820:Hyaluronic Acid; D008274:Magnesium