Necdin modulates osteogenic cell differentiation by regulating Dlx5 and MAGE-D1

Osteoblasts originate from mesenchymal stem cells that also differentiate into adipocytes, myoblasts, chondrocytes and fibroblasts. Osteogenic differentiation involves diverse regulatory proteins, including transcription and growth factors. Neurally differentiated embryonal carcinoma-derived protein (Necdin) has been identified as a key regulator of cell differentiation in various tissues, including neuronal, adipose, and muscular tissues; although its role in bone tissue remains to be established. Here, we investigated the potential involvement of Necdin in osteogenic differentiation. Our experiments revealed high expression of Necdin during osteoblast differentiation. Moreover, both transient and stable expression of Necdin induced osteoblast-specific markers in an osteogenic cell line through formation of a complex with melanoma-associated antigen D1 (MAGE-D1) and distal-less Homeobox 5 (Dlx5) and Runx2 promoter activation. Necdin expression was further associated with suppression of both cell proliferation and death in osteoblasts. Our results suggest that Necdin plays roles in cellular differentiation, proliferation and death in bone tissue. - Highlights: • Necdin is highly expressed during osteoblast differentiation. • Necdin induces expression of osteoblast-specific markers in osteogenic cells. • Necdin forms complex with MAGE-D1 and Dlx5, and induces Runx2 promoter activation. • Necdin plays important roles in osteoblastic differentiation.