title: Organization of the Indian hedgehog--parathyroid hormone-related protein system in the postnatal growth plate.
abstract: In embryonic growth cartilage, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) participate in a negative feedback loop that regulates chondrocyte differentiation. Postnatally, this region undergoes major structural and functional changes. To explore the organization of the Ihh–PTHrP system in postnatal growth plate, we microdissected growth plates of 7-day-old rats into their constituent zones and assessed expression of genes participating in the h–PTHrP feedback loop. Ihh, Patched 1, Smoothened, Gli1, Gli2, Gli3, and Pthr1 were expressed in regions analogous to the expression domains in embryonic growth cartilage. However, PTHrP was expressed in resting zone cartilage, a site that differs from the embryonic source, the periarticular cells. We then used mice in which lacZ has replaced coding sequences of Gli1 and thus serves as a marker for active hedgehog signaling. At 1, 4, 8, and 12 weeks of age, lacZ expression was detected in a pattern analogous to that of embryonic cartilage. The findings support the hypothesis that the embryonic Ihh–PTHrP feedback loop is maintained in the postnatal growth plate except that the source of PTHrP has shifted to a more proximal location in the resting zone.
authors.affiliation: Growth and Cartilage Unit, Center for Molecular Medicine and Division of Pediatric Endocrinology, Department of Women’s and Children’s Health, Karolinska Institutet and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Chau
authors.forename: Patricia
authors.initials: P
authors.lastname: Forcinito
authors.forename: Anenisia C
authors.initials: AC
authors.lastname: Andrade
authors.forename: Anita
authors.initials: A
authors.lastname: Hegde
authors.forename: Sohyun
authors.initials: S
authors.lastname: Ahn
authors.forename: Julian C
authors.initials: JC
authors.lastname: Lui
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baron
authors.forename: Ola
authors.initials: O
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002356:Cartilage / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006132:Growth Plate / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009928:Organ Specificity; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D013977:Tibia / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D044162:Parathyroid Hormone-Related Protein; D001616:beta-Galactosidase