BMP Antagonism in Dura Mater and Its Role in Calvarial Healing

Stanford University, Stanford CA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Harnessing the mechanisms that underlie the regenerative capabilities of young animals to heal calvarial defects is important for developing alternative approaches to the repair of critical-sized calvarial defects. One such mechanism may be the balance between bone morphogenetic proteins (BMP) and its antagonist, Noggin, in dura mater. This molecular interaction has already been demonstrated to be important in regulating bone formation in osteoblasts and adipose-derived mesenchymal cells. Dura mater, especially from juvenile animals, not only provides strong paracrine signals directing osteogenesis, but may also be a source of new bone formation itself. I hypothesize that the regenerative potential of juvenile animals may be due in part to decreased BMP antagonism, in the form of Noggin, within the dura mater. This project will examine, in dural cell cultures, the effect of Noggin suppression, via siRNA, on adult dural cell proliferation and osteogenic differentiation. We will then study the effect of Noggin suppression on healing of adult calvarial defects, via fibrin gel delivery of siRNA to the dura mater underlying the defect. Calvarial defects pose a serious challenge for craniofacial surgeons. Skull defects also pose a signficant socioeconomic burden on our healthcare infrastructure. Current clinical approaches to reconstructing calvarial defects include the use of autogenous grafts, allogenic materials, and prosthetic products, each with its inherent disadvantages. The ability to harness the regenerative potential of juvenile calvaria portends an exciting and novel method of repairing adult skull defects. [unreadable] [unreadable] [unreadable]