title: Chondrogenesis, bone morphogenetic protein-4 and mesenchymal stem cells.
abstract: OBJECTIVE
  As adult cartilage has very limited potential to regenerate, cartilage repair is challenging. Available treatments have several disadvantages, including formation of fibrocartilage instead of hyaline-like cartilage, as well as eventual ossification of the newly formed tissue. The focus of this review is the application of bone morphogenetic protein-4 (BMP-4) and mesenchymal stem cells (MSCs) in cartilage repair, a combination that could potentially lead to the formation of permanent hyaline-like cartilage in the defect.
  
  
  METHODS
  This review is based on recent literature in the orthopaedic and tissue engineering fields, and is focused on MCSs and bone morphogenetic proteins (BMPs).
  
  
  RESULTS
  BMP-4, a stimulator of chondrogenesis, both in vitro and in vivo, is a potential therapeutic agent for cartilage regeneration. BMP-4 delivery can improve the healing process of an articular cartilage defect by stimulating the synthesis of the cartilage matrix constituents: type II collagen and aggrecan. BMP-4 has also been shown to suppress chondrogenic hypertrophy and maintain regenerated cartilage. Use of an appropriate carrier for BMP-4 is crucial for successful reconstruction of cartilage defects. Due to the relatively short half-life in vivo of BMP-4, there is a need to localize and maintain the delivery of BMP-4 to the injury site. Additionally, the delivery of MSCs to the wound site could improve cartilage regeneration; therefore, the carrier should function both as a cell and a protein delivery vehicle.
  
  
  CONCLUSIONS
  The role of BMP-4 in chondrogenesis is significant, and successful methods to deliver BMP-4, with or without MSCs, to the cartilage defect site are a promising therapy to treat cartilage defects.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Miljkovic
authors.forename: G M
authors.initials: GM
authors.lastname: Cooper
authors.forename: K G
authors.initials: KG
authors.lastname: Marra
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism*; D020219:Chondrogenesis / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*
chemical_list: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins