Stimulation of interleukin-4 of cell proliferation and mRNA expression of alkaline phosphatase and collagen type I in human osteoblast-like cells of trabecular bone.
Interleukin-4 (IL-4) potently inhibits bone resorption by preventing the differentiation of osteoclast precursors to osteoclasts. To elucidate the role of IL-4 in bone formation, we studied the effects of human IL-4 on human osteoblast-like cells obtained from trabecular bone, which showed increased osteocalcin production in response to 1,25-(OH)2D3 in more than 10 passages. IL-4 stimulated the proliferation of osteoblast-like cells in a concentration-dependent manner, showing the minimal and maximal stimulatory effects at 10 pg/ml and 100-1000 pg/ml, respectively. IL-4 also stimulated the expression of alkaline phosphatase mRNA (1.7-fold) and the enzyme activity to the same extent at 10-100 pg/ml. Furthermore, IL-4 stimulated collagen type I mRNA expression in human osteoblast-like cells. The cytokine did not affect osteocalcin production in a short culture period (3 days). These in vitro findings suggest that IL-4, a bone-resorption-inhibitory cytokine produced by activated T cells in bone marrow, may exert an anabolic effect on osteoblast-like cells in trabecular bone through a paracrine mechanism.
Nohtomi
K
K
Research Institute for Growth Science, Tokyo, Japan.
Sato
K
K
Shizume
K
K
Yamazaki
K
K
Demura
H
H
Hosoda
K
K
Murata
Y
Y
Seo
H
H
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D001846:Bone Development / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology
D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015675:Osteocalcin; D015847:Interleukin-4; D003094:Collagen; D000469:Alkaline Phosphatase; D002117:Calcitriol