title: Cell and matrix modulation in prenatal and postnatal equine growth cartilage, zones of Ranvier and articular cartilage.
abstract: Formation of synovial joints includes phenotypic changes of the chondrocytes and the organisation of their extracellular matrix is regulated by different factors and signalling pathways. Increased knowledge of the normal processes involved in joint development may be used to identify similar regulatory mechanisms during pathological conditions in the joint. Samples of the distal radius were collected from prenatal and postnatal equine growth plates, zones of Ranvier and articular cartilage with the aim of identifying Notch signalling components and cells with stem cell-like characteristics and to follow changes in matrix protein localisation during joint development. The localisation of the Notch signalling components Notch1, Delta4, Hes1, Notch dysregulating protein epidermal growth factor-like domain 7 (EGFL7), the stem cell-indicating factor Stro-1 and the matrix molecules cartilage oligomeric matrix protein (COMP), fibromodulin, matrilin-1 and chondroadherin were studied using immunohistochemistry. Spatial changes in protein localisations during cartilage maturation were observed for Notch signalling components and matrix molecules, with increased pericellular localisation indicating new synthesis and involvement of these proteins in the formation of the joint. However, it was not possible to characterise the phenotype of the chondrocytes based on their surrounding matrix during normal chondrogenesis. The zone of Ranvier was identified in all horses and characterised as an area expressing Stro-1, EGFL7 and chondroadherin with an absence of COMP and Notch signalling. Stro-1 was also present in cells close to the perichondrium, in the articular cartilage and in the fetal resting zone, indicating stem cell-like characteristics of these cells. The presence of stem cells in the articular cartilage will be of importance for the repair of damaged cartilage. Perivascular chondrocytes and hypertrophic cells of the cartilage bone interface displayed positive staining for EGFL7, which is a novel finding and suggests a role of EGFL7 in the vascular infiltration of growth cartilage.
authors.affiliation: Section of Pathology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Löfgren
authors.forename: Stina
authors.initials: S
authors.lastname: Ekman
authors.forename: Emilia
authors.initials: E
authors.lastname: Svala
authors.forename: Anders
authors.initials: A
authors.lastname: Lindahl
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ley
authors.forename: Eva
authors.initials: E
authors.lastname: Skiöldebrand
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000254:growth & development*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D006132:Growth Plate / Q000166:cytology*; D006706:Homeostasis; D006736:Horses / Q000254:growth & development*
chemical_list: D015415:Biomarkers
keywords: EGFL7; Notch signalling; Stro-1; extracellular matrix; horse