PMID- 10208865
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20190612
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 257
IP  - 3
DP  - 1999 Apr 21
TI  - Indian hedgehog in the late-phase differentiation in mouse chondrogenic EC cells,
      ATDC5: upregulation of type X collagen and osteoprotegerin ligand mRNAs.
PG  - 814-20
AB  - Endochondral bone formation includes a cascade of cellular events such as
      proliferation, maturation, hypertrophic conversion and calcification of
      chondrocytes and the cartilage replacement by bone. During these processes,
      hypertrophic conversion and calcification of chondrocytes (the late-phase
      differentiation) is a crucial process of chondrogenic differentiation. Indian
      hedgehog (Ihh), a secreted protein expressed in early hypertrophic chondrocytes, 
      is thought to be involved in regulation of hypertrophic conversion via a feedback
      loop through the perichondrium. In the present study, we showed by Northern
      analysis and in situ hybridization that Smoothened (Smo), a key component in
      hedgehog signal transduction, was expressed in chondrocytes in both adult mice
      and mouse embryos at 16 days post-coitum in vivo, suggesting that Ihh directly
      acts on chondrocytes. We previously reported that Ihh, Patched and Smo were all
      expressed in differentiated ATDC5 cells. Exogenously administered mouse
      recombinant N-terminal protein of Ihh (mrIhh-N) upregulated the gene expression
      of type X collagen, a phenotypic marker of hypertrophic chondrocytes, as well as 
      osteoprotegerin ligand (OPGL), a potent stimulator of osteoclastogenesis and
      osteoclast activity, while it did not modulate the expression of Ihh itself, bone
      morphogenetic protein (BMP)-4, BMP-6, transforming growth factor (TGF)-beta1 and 
      TGF-beta2 in differentiated ATDC5 cells. Moreover, when added to the osteoclast
      cultures, mrIhh-N markedly stimulated the formation of resorption pits on dentine
      slices. Our data support the hypothesis that Ihh stimulated the late-phase
      chondrogenic differentiation in differentiated ATDC5 cells and upregulated the
      gene expression of OPGL in these cells.
CI  - Copyright 1999 Academic Press.
FAU - Akiyama, H
AU  - Akiyama H
AD  - Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of
      Medicine, Kyoto University, Kyoto, Sakyo, 606-8507, Japan.
      akiy@kuhp.kyoto-u.ac.jp
FAU - Shigeno, C
AU  - Shigeno C
FAU - Iyama, K
AU  - Iyama K
FAU - Ito, H
AU  - Ito H
FAU - Hiraki, Y
AU  - Hiraki Y
FAU - Konishi, J
AU  - Konishi J
FAU - Nakamura, T
AU  - Nakamura T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Patched Receptors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proteins)
RN  - 0 (RANK Ligand)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Smo protein, mouse)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Tnfrsf11a protein, mouse)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Alveolar Bone Loss
MH  - Animals
MH  - Bone Morphogenetic Proteins/genetics
MH  - Carrier Proteins/*genetics
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Chondrocytes/*cytology/drug effects/metabolism
MH  - Collagen/*genetics
MH  - Dentin/drug effects
MH  - Embryo, Mammalian/cytology/metabolism
MH  - Hedgehog Proteins
MH  - Intracellular Signaling Peptides and Proteins
MH  - Membrane Glycoproteins/*genetics
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Osteoclasts/drug effects/physiology
MH  - Patched Receptors
MH  - Peptide Fragments/genetics/pharmacology
MH  - Proteins/genetics/*pharmacology
MH  - RANK Ligand
MH  - RNA, Messenger/*metabolism
MH  - Rabbits
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Receptors, Cell Surface/genetics
MH  - *Receptors, G-Protein-Coupled
MH  - Recombinant Proteins/pharmacology
MH  - Smoothened Receptor
MH  - *Trans-Activators
MH  - Transforming Growth Factor beta/genetics
MH  - Up-Regulation/*drug effects
EDAT- 1999/04/20 00:00
MHDA- 1999/04/20 00:01
CRDT- 1999/04/20 00:00
PHST- 1999/04/20 00:00 [pubmed]
PHST- 1999/04/20 00:01 [medline]
PHST- 1999/04/20 00:00 [entrez]
AID - S0006291X99904941 [pii]
AID - 10.1006/bbrc.1999.0494 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Apr 21;257(3):814-20. doi:
      10.1006/bbrc.1999.0494.