title: A new strategy to tackle severe knee osteoarthritis: Combination of intra-articular and intraosseous injections of Platelet Rich Plasma.
abstract: BACKGROUND
  Knee osteoarthritis (KOA) is a mechanically induced, cytokine and enzyme-mediated disorder involving all the joint tissue of the knee. Rebuilding a physiological-homeostatic network at the tissue level following knee organ failure, such as in severe KOA, is a daunting task with therapeutic targets encompassing the articular cartilage, synovium and subchondral bone. Intraarticular infiltration of plasma rich in growth factors (PRP) has emerged as a promising symptomatic approach, although it is insufficient to reach the subchondral bone.
  
  
  METHODS
  This review addresses current molecular and cellular data in joint homeostasis and osteoarthritis pathophysiology. In particular, it focuses on changes that subchondral bone undergoes in knee osteoarthritis and evaluates recent observations on the crosstalk among articular cartilage, subchondral bone and synovial membrane. In addition, we review some mechanistic aspects that have been proposed and provide the rationale for using PRP intraosseously in KOA.
  
  
  CONCLUSIONS
  The knee joint is a paradigm of autonomy and connectedness of its anatomical structures and tissues from which it is made. We propose an innovative approach to the treatment of severe knee osteoarthritis consisting of a combination of intraarticular and intraosseous infiltrations of PRP, which might offer a new therapeutic tool in KOA therapy.
authors.affiliation: a Arthroscopic Surgery Unit , Hospital Vithas San José , Vitoria-Gasteiz , Spain.
authors.forename: Mikel
authors.initials: M
authors.lastname: Sánchez
authors.affiliation: b Department of Regenerative Medicine, Laboratory of Regenerative Medicine, BTI Biotechnology Institute , Vitoria , Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Anitua
authors.affiliation: c Arthroscopic Surgery Unit Research , Hospital Vithas San José , Vitoria-Gasteiz , Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Delgado
authors.affiliation: c Arthroscopic Surgery Unit Research , Hospital Vithas San José , Vitoria-Gasteiz , Spain.
authors.forename: Peio
authors.initials: P
authors.lastname: Sanchez
authors.affiliation: b Department of Regenerative Medicine, Laboratory of Regenerative Medicine, BTI Biotechnology Institute , Vitoria , Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Prado
authors.affiliation: d Departamento Fisiología, Facultad de Medicina , UPV , Leioa , Spain.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Goiriena
authors.affiliation: e Cell Therapy Program, Foundation for Applied Medical Research , University of Navarra , Pamplona , Spain.|f Hematology and Cell Therapy Department , Clínica Universidad de Navarra, University of Navarra , Pamplona , Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.affiliation: b Department of Regenerative Medicine, Laboratory of Regenerative Medicine, BTI Biotechnology Institute , Vitoria , Spain.|g Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy , University of the Basque Country , Vitoria , Spain.|h Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine , CIBER-BBN, SLFPB-EHU , Vitoria-Gasteiz , Spain.
authors.forename: Gorka
authors.initials: G
authors.lastname: Orive
authors.affiliation: b Department of Regenerative Medicine, Laboratory of Regenerative Medicine, BTI Biotechnology Institute , Vitoria , Spain.
authors.forename: Sabino
authors.initials: S
authors.lastname: Padilla
mesh_terms: D006801:Humans; D017148:Infusions, Intraosseous; D007270:Injections, Intra-Articular; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D007719:Knee Joint; D020370:Osteoarthritis, Knee / Q000628:therapy*; D053657:Platelet-Rich Plasma
chemical_list: D036341:Intercellular Signaling Peptides and Proteins
keywords: Knee osteoarthritis; biological treatment; plasma rich in growth factors; subchondral bone