Modulation of Growth Factor/Cytokine Synthesis and Signaling by 1α,25-Dihydroxyvitamin D3: Implications in Cell Growth and Differentiation

Abstract

AbstractDistinct from its classic functions in the regulation of calcium and phosphorus metabolism as a systemic hormone, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is involved in the local control and regulation of cellular growth and differentiation in various tissues, including epidermis (keratinocytes) and bone (osteoblasts and osteoclasts). In this review, the impact of 1α,25(OH)2D3 on growth factor/cytokine synthesis and signaling is discussed, particularly as it pertains to bone cells and keratinocytes. 1α,25(OH)2D3 not only regulates growth factor/cytokine synthesis but may also alter growth factor signaling. Recently discovered examples for such interactions are the interactions between the vitamin D receptor and the mothers against decapentaplegic-related proteins that function downstream of TGFβ receptors. Inhibitory effects of 1α,25(OH)2D3 on keratinocytes through TGFβ activation and IL-1α, IL-6, and IL-8 suppression may provide a rationale for its beneficial effects in the treatment of hyperproliferative skin disorders, whereas stimulatory effects through the epidermal growth factor-related family members and platelet-derived growth factor may be operative in its beneficial effects in skin atrophy and wound healing. Modulation of cytokines and growth factors by 1α,25(OH)2D3 during bone remodeling plays an important role in the coupling of osteoblastic bone formation with osteoclastic resorption to maintain bone mass.