title: CDMP1/GDF5 has specific processing requirements that restrict its action to joint surfaces.
abstract: CDMP1/GDF5 has not demonstrated biological activity in Xenopus embryos when overexpressed by mRNA injection. We provide biological and biochemical evidence that to become active, the protein requires cleavage by two distinct proteolytic enzymes. We demonstrate a specific overlap in the expression patterns of CDMP1/GDF5 with the proteases required to release the mature peptide at the location of the future articular surface but not in the future joint space. Taken together, these observations provide a plausible mechanism for local action of CDMP1/GDF5 consistent with requirements imposed by current models of pattern formation in the developing limb.
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland 20892, USA. john.thomas@fda.hhs.gov
authors.forename: J Terrig
authors.initials: JT
authors.lastname: Thomas
authors.forename: David
authors.initials: D
authors.lastname: Prakash
authors.forename: Karis
authors.initials: K
authors.lastname: Weih
authors.forename: Malcolm
authors.initials: M
authors.lastname: Moos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D005121:Extremities / Q000033:anatomy & histology / Q000196:embryology; D045683:Furin / Q000235:genetics / Q000378:metabolism; D055428:Growth Differentiation Factor 5; D006801:Humans; D007596:Joints / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D045702:Proprotein Convertase 5 / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013499:Surface Properties; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5; D045702:Proprotein Convertase 5; D045683:Furin