1,25-Dihydroxy vitamin D3 stimulation of TGF-beta expression in chick embryonic calvarial bone.
Bone is a highly active producer of the cytokine, transforming growth factor-beta (TGF-beta), which is likely to be functionally involved in the regulation and maintenance of bone development and growth. In addition, bone functions are also regulated by the major calciotropic hormone, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3). This investigation aims to examine the possible relationship between TGF-beta and 1,25(OH)2D3 using an unique calcium-deficient chick embryonic model. By means of long-term culture without the eggshell (shell-less or SL culture), chick embryos may be rendered severely calcium-deficient with gross undermineralization of the skeleton. We have previously observed that the calvaria of these SL embryos develop abnormal chondrogenic phenotype, with production of collagen type II, and elevated TGF-beta expression. Administration of 1,25(OH)2D3 to the SL embryos in vivo on incubation days 10 and 12 (SL + D embryos) resulted in near-normal serum calcium on day 14 and improved calvarial calcification. However, TGF-beta expression in the SL + D calvaria was further increased compared to untreated SL calvaria, when analyzed at both the mRNA and protein levels. Histolocalization of gene expression by immunohistochemistry and in situ hybridization revealed that cells in the less mineralized orbital and temporal zones of the calvarium are particularly affected by the 1,25(OH)2D3 treatment. Interestingly, the increased TGF-beta expression resulting from 1,25(OH)2D3 treatment did not correct the aberrant collagen phenotype in the SL calvaria. These observations suggest that TGF-beta expression by bone cells in situ is stimulated by 1,25(OH)2D3, and that normal cellular differentiation and morphogenesis of the embryonic calvaria are dependent on proper and balanced TGF-beta expression as well as the state of tissue mineralization.
Sato
T
T
Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107.
Ono
T
T
Tuan
R S
RS
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002642:Chick Embryo; D003094:Collagen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D012886:Skull / Q000737:chemistry / Q000187:drug effects* / Q000196:embryology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000187:drug effects* / Q000235:genetics*
D016212:Transforming Growth Factor beta; D003094:Collagen; D002117:Calcitriol; D002118:Calcium