Poster Sessions

CYT-2

Mitsuaki Ono

M. Ono, C. Inkson, M. F. Young

Wnt-induced Secreted Protein-1 (WISP-1)/CCN4 Potentially Regulates Bone by Controlling Osteogenic Differentiation through BMP-2

Objectives: WISP-1/CCN4 is expressed in developing bone and is up-regulated during fracture repair. The goal of this study was to determine the role of WISP-1 in controlling bone cell and tissue function. Methods and Results: To test the role of WISP-1 in vivo transgenic mice were made to express WISP-1 in bones using the 2.4 KB Col1A1 promoter. The bone mineral density (BMD) was assessed by a Pixumus DEXA scanner. The transgenic mice had a small but significant increase in BMD compared to wild-type controls (10% increase; p<0.05). To determine the mechanism causing this increase in BMD the effects of WISP-1 were tested using hBMSC infected with adenovirus to WISP-1 and BMP2 separately or in combinations. Osteogenic differentiation was assessed using alizarin red accumulation or by qRT-PCR of mRNA for alkaline phosphatase (ALP) or osteopontin (OPN). WISP-1 by itself modestly increased osteogenic differentiation in vitro. Interestingly treatment with both WISP-1 with BMP-2 induced significantly higher expression of ALP and OPN mRNA than with either WISP-1 or BMP-2 alone. Conclusion: WISP-1 has a positive influence on bone formation and may work by enhancing the effects of BMP-2 to increase osteogenesis.