AbstractMarine sponges have been known to provide a source of novel bone and cartilage replacements because of their secondary metabolites and specific skeleton structures. In particular, it has been reported that spongin as a component of fibrous skeleton, pseudokeratin, neurokeratin, horny protein, and collagen‐like protein in sponges can be used in several biomedical applications including osteoarthritis (OA). However, the pharmacological mechanism of action of spongin remains obscure. In this study, it was investigated whether spongin derived from Hymeniacidon sinapium can promote bone mineralization of osteoblast‐like MG‐63 cells. Our present study provides the first evidence that spongin is effective in activating bone mineralization. Furthermore, spongin increased ALP activity, collagen synthesis, and osteocalcin secretion in addition to bone mineralization in osteoblastic cells in vitro. In addition, it was demonstrated that spongin exerted the inhibitory effect on production of inflammatory mediators such as TNF‐α, IL‐1β, and PGE2 in macrophage, RAW264.7 cells. These results suggest that the anti‐inflammatory effect of spongin derived from Hymeniacidon sinapium can play a critical role in bone mineralization of osteoblast‐like MG‐63 cells. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009