title: Fibroblast growth factor 23 and Klotho are present in the growth plate.
abstract: BACKGROUND
  Regulation of phosphate homeostasis is essential for mineralization and enchondral ossification. Fibroblast growth factor 23 (FGF23) and its obligatory co-receptor Klotho (KL) play a key role in this process by influencing both renal phosphate reabsorption and vitamin D metabolism. In disease, excessive action of FGF23 leads to hypophosphatemic rickets, while its deficiency causes tumoral calcinosis. Although osteocytes and osteoblasts are widely seen as the primary source of FGF23 under physiological conditions, the origin of systemic FGF23 remains controversial. In this study, we investigated the expression of FGF23 and KL in porcine growth plate cartilage, adjacent tissues, and parenchymal tissues.
  
  
  METHODS
  Tissue samples were obtained from 4- to 6-week-old piglets. mRNA expression was quantified by real-time PCR and normalized to 18S rRNA. Immunohistochemical staining was performed for FGF23, KL, collagen type X, and FGF receptor 1. Growth plate chondrocyte subpopulations were acquired by collagenase digestion of growth plate explants and subsequent density gradient centrifugation.
  
  
  RESULTS
  We could detect both FGF23 and KL mRNA and protein in growth plate chondrocytes. FGF23 expression was mainly found in hypertrophic and resting chondrocytes. Furthermore, significant expression of both genes was observed in bone, liver, and spleen.
  
  
  CONCLUSIONS
  These data challenge previous expression analyses, in particular theories of bone as the exclusive source of FGF23. Moreover, significant expression of FGF23 and KL within the growth plate and adjacent tissues imply a potential local role of FGF23 in chondrocyte differentiation and tissue mineralization.
authors.affiliation: Department of Pediatrics & Adolescent Medicine, Medical University Vienna, Vienna, Austria. adalbert.raimann@meduniwien.ac.at
authors.forename: Adalbert
authors.initials: A
authors.lastname: Raimann
authors.forename: Diana Alexandra
authors.initials: DA
authors.lastname: Ertl
authors.forename: Magdalena
authors.initials: M
authors.lastname: Helmreich
authors.forename: Susanne
authors.initials: S
authors.lastname: Sagmeister
authors.forename: Monika
authors.initials: M
authors.lastname: Egerbacher
authors.forename: Gabriele
authors.initials: G
authors.lastname: Haeusler
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D024121:Collagen Type X / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D000090265:Klotho Proteins; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015203:Reproducibility of Results; D013194:Staining and Labeling; D034421:Sus scrofa
chemical_list: D024121:Collagen Type X; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins