Effect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes.
AffiliationDepartment of Dermatology, Osaka University School of Medicine, Japan.
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CitationEffect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes. 1990, 17 (2):97-103 J. Dermatol.
JournalThe Journal of dermatology
AbstractThe effect of 1,24R-dihydroxyvitamin D3 (1,24R(OH)2D3), a synthetic analogue of a biologically active form of vitamin D3 (1,25-dihydroxyvitamin D3, 1,25(OH)2D3), on the growth of human keratinocytes cultured in serum-free medium was investigated. The growth of cultured normal human keratinocytes was inhibited by 65% by 10(-8)M 1,24R(OH)2D3 and by 90% by 10(-7)M 1,24(OH)2D3. It inhibited cell growth almost completely at 10(-6)M. The DNA synthesis of keratinocytes was also inhibited with 1,24R(OH)2D3 by 27% at 10(-8)M, 59% at 10(-7)M, and 92% at 10(-6)M. The inhibition of cell growth and DNA synthesis were more remarkable by 1,24R(OH)2D3 than by 1,25(OH)2D3. 1,24R(OH)2D3 also inhibited the growth of keratinocytes derived from patients with psoriasis vulgaris; the growth inhibitory effect was again more remarkable with 1,24R(OH)2D3 than with 1,25(OH)2D3. The viability and protein synthesis of keratinocytes were not affected by 1,24R(OH)2D3, suggesting that the growth inhibitory effect is due to its biological activity, not to cytotoxicity. The binding of [3H]-labeled 1,25(OH)2D3 to its receptor in the cytosolic fraction of cultured keratinocytes was competitively substituted by unlabeled 1,24R(OH)2D3 as well as 1,25(OH)2D3, suggesting that 1,24R(OH)2D3 binds to the 1,25(OH)2D3 receptor. It was found that the affinity of 1,24R(OH)2D3 for the receptor was slightly higher than that of 1,25(OH)2D3. These results demonstrate that 1,24R(OH)2D3 functions as a potent growth inhibitor in vitro in human keratinocytes from both normal and psoriatic epidermis, and it possesses a higher affinity for the 1,25(OH)2D3 receptor in cultured human keratinocytes. The difference in affinity of 1,24R(OH)2D3 for the 1,25(OH)2D3 receptor correlates with its greater inhibition of keratinocyte growth than 1,25(OH)2D3. 1,24R(OH)2D3 may be useful in the treatment of psoriasis.
- 1 alpha,24R-dihydroxyvitamin D3 has an ability comparable to that of 1 alpha,25-dihydroxyvitamin D3 to induce keratinocyte differentiation.
- Authors: Kobayashi T, Okumura H, Azuma Y, Kiyoki M, Matsumoto K, Hashimoto K, Yoshikawa K
- Issue date: 1990 Nov
- Involvement of endogenously produced 1,25-dihydroxyvitamin D-3 in the growth and differentiation of human keratinocytes.
- Authors: Matsumoto K, Azuma Y, Kiyoki M, Okumura H, Hashimoto K, Yoshikawa K
- Issue date: 1991 May 17
- Growth-inhibitory effects of 1,25-dihydroxyvitamin D3 on normal and psoriatic keratinocytes.
- Authors: Hashimoto K, Matsumoto K, Higashiyama M, Nishida Y, Yoshikawa K
- Issue date: 1990 Jul
- 1,24(R)-dihydroxyvitamin D3, a novel active form of vitamin D3 with high activity for inducing epidermal differentiation but decreased hypercalcemic activity.
- Authors: Matsunaga T, Yamamoto M, Mimura H, Ohta T, Kiyoki M, Ohba T, Naruchi T, Hosoi J, Kuroki T
- Issue date: 1990 Mar
- Specific binding of 24R,25-dihydroxyvitamin D3 to chick intestinal mucosa: 24R,25-dihydroxyvitamin D3 is an allosteric effector of 1,25-dihydroxyvitamin D3 binding.
- Authors: Wilhelm F, Ross FP, Norman AW
- Issue date: 1986 Aug 15