Bone Biology
In order to complement our work in cranial suture biology, distraction osteogenesis, and calvarial re-ossification, the bone group also investigates fundamental aspects of osteogenesis and bone formation with emphasis on angiogenesis. The goal of this work is to understand how osteoblast can form bone in very different environments (e.g. cranial suture, mandible, or calvarial bone plates). For example, we have demonstrated that FGF-2 induces osteoblasts to produce VEGF (a potent angiogenic factor) as well as BMP-2 (a potent osteogenic factor). In conjunction with our in vivo model, we are learning that successful bone formation requires precise regulation of angiogenesis and osteogenesis. Ultimately, we believe that learning to manipulate osteoblast biology will lead to improve clinical outcomes.
Spector JA, Mehrara BJ, Luchs JS, Greenwald JA, Faganhol PS, Saadeh PB, Steinbrech DS, Longaker MT: Expression of Adenovirally Delivered Gene Products in Healing Osseous Tissues. Ann Plast Surg 44: 522-528, 2000.
Mehrara BJ, Saadeh PB, Steinbrech DS, Dudziak M, Spector JA, Greenwald JA, Gittes GK, Longaker MT: Adenvirus-Mediated Gene Therapy of Osteoblasts In Vitro and In Vivo. J Bone Mineral Research 14: 1290-1301, 1999.
Steinbrech DS, Mehrara BJ, Rowe NM, Dudziak ME, Luchs JS, Saadeh PB, Gittes GK, Longaker MT: “Gene Expression of TGF-Beta, TGF-Beta Receptor, and Extracelluar Matric Protein During Membraneous Bone Healing in Rats. Plast Reconstr Surg 105: 2028-2038, 2000.
Steinbrech DS, Mehrara BJ, Saadeh PB, Greenwald JA, Spector JS, Gittes GK, Longaker MT: Hypoxia Increases Insulin-like Growth Factor Gene Expression in Rat Osteoblast. Ann Plast Surg 44: 529-534, 2000.
Steinbrech DS, Mehrara BJ, Rowe NM, Dudziak ME, Saadeh PB, Gittes GK, Longaker MT: Gene Expression of Insulin-like Growth Factor I and II in Rat Membranous Osteotomy Healing. Ann Plast Surg 42: 481-487, 1999.
Saadeh PB, Mehrara BJ, Steinbrech DS, Spector JA, Greenwald JA, Chin GS, Ueno H, Gittes GK, Longaker MT: Mechanisms of Fibroblast Growth Factor-2 Modulation of Vascular Endothelial Growth Factor Expression by Osteoblastic Cells. Endocrinology 141: 2075-2083, 2000.
Steinbrech DS, Mehrara BJ, Saadeh PB, Greenwald JA, Spector JA, Gittes GK, Longaker MT: VEGF Expression in an Osteoblast-like Cell Line is Regulated by a Hypoxia Response Mechanism. Am J Physiology 278: 853-860, 2000.
Saadeh PB, Mehrara BJ, Steinbrech DS, Dudziak ME, Greenwald JA, Luchs JS, Spector JA, Ueno H, Gittes GK, Longaker MT: Transforming Growth Factor-Beta 1 Modulates the Expression of Vascular Endothelial Growth Factor by Osteoblasts. Am J Physiology 277: 628-637, 1999.
Steinbrech DS, Mehrara BJ, Saadeh PB, Chin GS, Dudziak ME, Gerrets RP, Gittes GK, Longaker MT: Hypoxia Regulates VEGF Expression and Cellular Regulation by Osteoblasts In Vitro. Plast Reconstr Surg 104: 738-747, 1999.</p>
Spector JA, Mehrara BJ, Greenwald JA, Saadeh PB, Steinbrech DS, Bouletreau PJ, Smith LP, Longaker MT: Osteoblast Expression of Vascular Endothelial Growth Factor is Modulated by the Extracellular Microenvironment. Am J Physiology 280: C72-80, 2001.
Paccione MF, Warren SM, Spector JA, Greenwald JA, Longaker MT: A Mouse Model of Mandibular Healing. J Craniofac Surg (Accepted for Publication).
Bouletreau PJ, Steinbrech DS, Spector JA, Warren SM, Greenwald JA, Mehrara BJ, Detch RC, Longaker MT: Gene Expression of Transforming Growth Factor Beta-3 and Tissue Inhibitor of Matalloproteinase-1 During Membranous Bone Healing in Rats. J Craniofac Surg 11: 521-526, 2000.
Spector JA, Luchs JS, Mehrara BJ, Greenwald JA, Smith LP, Longaker MT: Expression of Bone Morphogenetic Proteins during Memebranous Bone Healing. Plast Reconstr Surg 107: 124-134, 2001
Fagenholz PJ, Warren SM, Greenwald JA, Bouletreau PJ, Spector JA, Crisera FE, Longaker MT: Osteoblast Gene Regulation is Differentially Regulated by TGF-B Isoforms. J Craniofac Surg 12: 183-190, 2001
Warren SM, Steinbrech DS, Mehrara BJ, Saadeh PB, Greenwald JA, Spector JA, Bouletreau PJ, Longaker MT: Hypoxia regulates osteoblast gene expression. J Surg Res 99: 147-155, 2001.
