Evaluate Therapy Strategies for Osteogenesis and Angiogenesis of Posterolateral Spinal Fusion Basing on the Specificity of Biomaterials and Mscs from Osteoporotic Patients

Osteoporosis is a multifactorial disease with genetic, nutritional, aging, and hormonal components. MSCs from control and osteoporotic women showed differences in their capacity to differentiate into the osteogenic and adipogenic pathways. In osteoporosis, increased bone marrow adipocyte production is counterbalanced by diminished production of osteogenic cells. Leptin is a 16-kDa peptide hormone product of the ob (Lep) gene. Leptin receptors (Leptin-R) are expressed on the surface of human MSCs. Leptin has a significant effect of promoting osteogenesis and inhibiting adipogenesis in MSCs. Leptin activity in MSCs from osteoporotic women appears hampered, , suggesting that inadequate leptin activity contributes to excessive lipid accumulation in bone marrow. SIRT1, a mammalian homolog of Sir2 (silent information regulator 2), functions as a NAD+ dependent class 3 histone deacetylase and is essential for cell survival and increased longevity in mammalian cells. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of MSCs also has been reported. Extracellular matrix (ECM) context is a critical element in controlling cellular function. Type I collagen has excellent biocompatibility and low immunogenicity as a biomaterial, and is widely used as a tissue scaffold for bone regeneration. Platelet-rich plasma (PRP) contains a number of growth factors in its natural composition and has relevance in clinical tissue engineering applications. However, PRP impairs the craniofacial bone repair associated with its elevated TGF-β levels also has been reported. The present study will use DNA microarray, real-time PCR, phospho-kinase array, western blotting techniques, and animal model to analysis genes and proteins expression during osteogenesis and angiogenesis of osteoporotic MSCs and EPCs which cultured in different combination of ECM matrix (collagen and PRP), osteoconductive materials (Interpore and HAP/β-TCP), and osteogenesis enhancer (leptin, and SIRT 1 activator : Resvertrol).

Project ID:PC10101-2086
External Project ID:NSC100-2314-B182-010-MY3