title: Human monoclonal antibody fragments targeting matrilin-3 in growth plate cartilage.
abstract: OBJECTIVE
  Many genetic disorders, including chondrodysplasias, and acquired disorders impair growth plate function, resulting in short and sometimes malformed bones. There are multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate, which could potentially be used to treat these disorders. Targeting these growth factors specifically to the growth plate might augment the therapeutic skeletal effect while diminishing undesirable effects on non-target tissues.
  
  
  METHODS
  Using yeast display technology, we selected single-chain variable antibody fragments that bound to human and mouse matrilin-3, an extracellular matrix protein specifically expressed in cartilage tissue. The ability of the selected antibody fragments to bind matrilin-3 and to bind cartilage tissue in vitro and in vivo was assessed by ELISA and immunohistochemistry.
  
  
  RESULTS
  We identified antibody fragments that bound matrilin-3 with high affinity and also bound with high tissue specificity to cartilage homogenates and to cartilage structures in mouse embryo sections. When injected intravenously in mice, the antibody fragments specifically homed to cartilage.
  
  
  CONCLUSIONS
  Yeast display successfully selected antibody fragments that are able to target cartilage tissue in vivo. Coupling these antibodies to chondrogenic endocrine and paracrine signaling molecules has the potential to open up new pharmacological approaches to treat childhood skeletal growth disorders.
authors.affiliation: Section on Growth and Development, National Institute of Child Health and Development, National Institutes of Health, Bldg. 10 CRC, Rm. 1-3330, 10 Center Drive, Bethesda, Maryland, 20892, USA.
authors.forename: Crystal Sao-Fong
authors.initials: CS
authors.lastname: Cheung
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Julian Chun-Kin
authors.initials: JC
authors.lastname: Lui
authors.forename: Dimiter
authors.initials: D
authors.lastname: Dimitrov
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baron
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D003001:Cloning, Molecular; D006132:Growth Plate / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007150:Immunohistochemistry; D064235:Matrilin Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D015003:Yeasts / Q000235:genetics
chemical_list: D007128:Immunoglobulin Fragments; D064235:Matrilin Proteins; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies