Vitamin D deficiency causes a selective reduction in deposition of transforming growth factor beta in rat bone: possible mechanism for impaired osteoinduction.
We demonstrated previously that implants of bone matrix prepared from vitamin D-deficient (-D) rats were less osteoinductive and contained less extractable mitogenic activity compared with control implants prepared from vitamin D-replete (+D) rats and proposed that bone from -D rats is deficient in one or more specific growth factors. To test this hypothesis, bones from rats that were fed either +D or -D diets and kept in the dark for 8 wk were extracted and assayed for insulin-like growth factors I and II (IGF-I and IGF-II) and transforming growth factor beta (TGF-beta), the three most abundant growth factors in rat bone, and osteocalcin. Serum calcium, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were determined at sacrifice. In -D rats, there were significant reductions in serum calcium, 25-hydroxyvitamin D3, and 1,25(OH)2D3 and skeletal TGF-beta but no differences in extractable skeletal protein, IGF-I, IGF-II, or osteocalcin compared with +D rats. To determine whether 1,25(OH)2D3 increased TGF-beta production by bone cells, we treated mouse calvaria for 6 days and mouse osteoblasts for 2 days with 10 nM 1,25(OH)2D3. Production of TGF-beta was increased almost 100% by 1,25(OH)2D3. We conclude that vitamin D deficiency reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could contribute to the previously observed decrease in osteoinduction in implants from -D rat bone. The findings support the possibility that vitamin D and bone-derived TGF-beta are required for normal repair of the skeleton.
Finkelman
R D
RD
Department of Periodontics, Loma Linda University, CA.
Linkhart
T A
TA
Mohan
S
S
Lau
K H
KH
Baylink
D J
DJ
Bell
N H
NH
D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D051381:Rats; D013002:Somatomedins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000378:metabolism*
D013002:Somatomedins; D016212:Transforming Growth Factor beta; D015675:Osteocalcin