Distribution of genes for parathyroid hormone (PTH)-related peptide, Indian hedgehog, PTH receptor and patched in the process of experimental spondylosis in mice.
OBJECTIVE
Little is known about the molecular mechanisms underlying the process of spondylosis. The authors determined the extent of genetic localization of major regulators of chondrogenesis such as Indian hedgehog (Ihh) and parathyroid hormone (PTH)-related peptide (PTHrP) and their receptors during the development of spondylosis in their previously established experimental mouse model.


METHODS
Experimental spondylosis was induced in 5-week-old ICR mice. The cervical spines were chronologically harvested, and histological sections were prepared. Messenger (m) RNA for PTHrP, Ihh, PTH receptor (PTHR; a receptor for PTHrP), patched (Ptc; a receptor for Ihh), bone morphogenetic protein (BMP)-6, and collagen type X (COL10; a marker for mature chondrocyte) was localized in the tissue sections by performing in situ hybridization. In the early stage, mRNA for COL10, Ihh, and BMP-6 was absent; however, mRNA for PTHrP, PTHR, and Ptc was detected in the anterior margin of the cervical discs. In the late stage, evidence of COL10 mRNA began to be detected, and transcripts for Ihh, PTHrP, and BMP-6 were localized in hypertrophic chondrocytes adjacent to the bone-forming area in osteophyte. Messenger RNA for Ptc and PTHR continued to localize at this stage. In control mice, expression of these genes was absent.


CONCLUSIONS
The localization of PTHrP, Ihh, BMP-6, and the receptors PTHR and Ptc demonstrated in the present experimental model indicates the possible involvement of molecular signaling by PTHrP (through the PTHR), Ihh (through the Ptc), and BMP-6 in the regulation of chondrocyte maturation leading to endochondral ossification in spondylosis.
Department of Orthopaedic Surgery, Osaka University Medical School, Suita, Japan. nakase@ort.med.osaka-u.ac.jp
Takanobu
T
Nakase
Kenta
K
Ariga
Wenxiang
W
Meng
Motoki
M
Iwasaki
Tetsuya
T
Tomita
Akira
A
Myoui
Kazuo
K
Yonenobu
Hideki
H
Yoshikawa
D000818:Animals; D024121:Collagen Type X / Q000235:genetics; D004195:Disease Models, Animal; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008813:Mice, Inbred ICR; D044162:Parathyroid Hormone-Related Protein; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone / Q000235:genetics*; D013128:Spinal Osteophytosis / Q000378:metabolism* / Q000473:pathology; D013131:Spine / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics*
D024121:Collagen Type X; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D044162:Parathyroid Hormone-Related Protein; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; C000606240:Ptch1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D015534:Trans-Activators