Distribution of genes for bone morphogenetic protein-4, -6, growth differentiation factor-5, and bone morphogenetic protein receptors in the process of experimental spondylosis in mice.
OBJECTIVE
Because little is known about the molecular mechanisms underlying the process of spondylosis, the authors examined the extent of genetic localization of several members of bone morphogenetic protein (BMP) and BMP receptors in chondrogenesis during the process of inducing spondylosis in their previously established experimental mice model.


METHODS
Experimental spondylosis was induced in 5-week-old ICR mice. The cervical spine was harvested chronologically, and histological sections were prepared. Messenger RNA for BMP-4, growth and differentiation (GDF)-5, BMP-6, and BMP receptors (ALK-3, -6, and BMP-RII) was localized in the tissue sections by in situ hybridization. In the early stage, BMP-4-derived mRNA was localized mainly in cells in the anterior margin of the cervical discs, together with ALK-6 and BMP-RII mRNA. No GDF-5 and BMP-6 mRNA was detected at this stage. In the late stage, cells positive for BMP-4 decreased, whereas GDF-5 and BMP-6 mRNA were localized in cells undergoing chondrogenesis. The ALK-3 mRNA began to appear in this stage, as did ALK-6 and BMP-RII.


CONCLUSIONS
The localization of transcripts for BMP-4, -6, and GDF-5 as well as BMP receptors shown during the present experimental model indicate the possible involvement of molecular signaling by these BMPs in the chondrogenic progress in spondylosis.
Nakase
T
T
Department of Orthopaedic Surgery, Osaka University Medical School, Suita, Japan. nakase@ort.med.osaka-u.ac.jp
Ariga
K
K
Miyamoto
S
S
Okuda
S
S
Tomita
T
T
Iwasaki
M
M
Yonenobu
K
K
Yoshikawa
H
H
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002574:Cervical Vertebrae / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020219:Chondrogenesis; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000235:genetics*; D017403:In Situ Hybridization; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017978:Receptors, Growth Factor; D013128:Spinal Osteophytosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014018:Tissue Distribution
C525810:Bmp4 protein, mouse; C525817:Bmp6 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D052004:Bone Morphogenetic Protein Receptors