epidermal-growth-factor and Fractures--Bone

This paper reviews the sequence of histomorphologic changes that occur in and around a fracture site, and discusses recent concepts about the roles of the cells and bone matrical moieties in promoting specific cell transformations during the phases of callus tissue formation and consolidation of the bony cortex. Current knowledge about the roles of autocrine, paracrine, and endocrine polypeptide growth and transforming factors lends new perspectives about this classic problem in bone physiology.

Topics: Animals; Bone and Bones; Bone Matrix; Bone Morphogenetic Proteins; Bone Resorption; Bony Callus; Cartilage; Epidermal Growth Factor; Fibroblast Growth Factors; Fibronectins; Fractures, Bone; Hematoma; Humans; Insulin-Like Growth Factor II; Macrophages; Osteoblasts; Osteoclasts; Osteogenesis; Parathyroid Hormone; Proteins; Stem Cells; Time Factors; Wound Healing

This study evaluates whether the combination of the rhBMP-2 and various types of growth factors including EGF, FGF, PDGF and VEGF increases osteoinductivity compared to the single use of rhBMP-2 through in vitro and in vivo study. Cultured human MSCs were treated with rhBMP-2 only or in combination with growth factors. For in vivo evaluation, rhBMP-2 only or with growth factors was implanted into the calvarial defect made on SD rats. Both EGF and PDGF significantly increased both ALP activity and expression level in hMSCs when treated in combination with rhBMP-2 at 3 and 7 days of differentiation and significantly raised the accumulation of the calcium at day 14. Furthermore, micro-CT scanning revealed that the EGF an FGF groups show significantly increased new bone surface ratio compared to the rhBMP-2 only group and, the EGF treatment significantly up regulated percent bone volume and trabecular number at two weeks after the surgery. VEGF treatment also significantly raised trabecular number and FGF treatment significantly increased the trabecular thickness. Histological examination revealed that the EGF combination group showed enhanced bone regeneration than the rhBMP-2 only group two weeks after the implantation. Even though the treatment of rhBMP-2 with PDGF and FGF failed to show enhanced osteogenesis in vitro and in vivo simultaneously, these results suggest that the positive effect of the combination of EGF and rhBMP-2 is expected to induce the bone formation earlier compared to the single use of rhBMP-2 in vitro and in vivo.

Topics: Animals; Bone Morphogenetic Protein 2; Epidermal Growth Factor; Fractures, Bone; Humans; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteogenesis; Rats; Rats, Sprague-Dawley; Recombinant Proteins

To explore the expression and significance of human epidermal growth factor (EGF) and nerve growth factor (NGF) in patients with knee osteoarthritis.. RT-PCR and enzyme-linked immunosorbent assay were used to measure the serum EGF and NGF expression levels of patients with limb fracture and brain trauma injurry after 1 d, 3 d, 7 d, 14 d and the relationship between them was analyzed. The level was compared among the simple fracture group, traumatic brain injury group and the normal control group, with 40 cases in each group.. The serum NGF levels were significantly different among three groups. Serum NGF, EGF mRNA and protein levels gradually decreased with the increasing injury time in the limb fracture combined with brain injury group, traumatic brain injury group, the simple fracture group and the health control group (P<0.05).. The serum of NGF, EGF levels significantly increased when limb fracture combined with brain injury, so EGF and NGF may be involved in the process of fracture healing.

Topics: Adult; Aged; Brain Injuries; Case-Control Studies; Chi-Square Distribution; Epidermal Growth Factor; Female; Fracture Healing; Fractures, Bone; Humans; Male; Middle Aged; Nerve Growth Factor; RNA, Messenger

Angiogenesis is a process stimulated in inflamed synovium of patients with osteoarthritis (OA), and contributes to the progression of the disease. Synovial fibroblasts secrete angiogenic factors, such as vascular endothelial growth factor (VEGF), an up-regulator of angiogenesis, and this ability is increased by interleukin (IL)-1beta. The purpose of this study was to verify whether IL-17 contributes and/or synergizes with IL-1beta and tumor necrosis factor (TNF)-alpha in vessel development in articular tissues by stimulating the secretion of proangiogenic factors by synovial fibroblasts.. We stimulated in vitro synovial fibroblasts isolated from OA, rheumatoid arthritis (RA) and fractured patients (FP) with IL-17 and IL-1beta and from OA patients with IL-17, IL-1beta and TNF-alpha. In the supernatants from the cultures, we assayed the amount of VEGF by immunoassay and other angiogenic factors (keratinocyte growth factor, KGF; hepatocyte growth factor, HGF; heparin-binding endothelial growth factor, HB-EGF; angiopoietin-2, Ang-2; platelet-derived growth factor B, PDGF-BB; thrombopoietin, TPO) by chemiluminescence; semiquantitative RT-PCR was used to state mRNA expression of nonreleased angiogenic factors (Ang-2 and PDGF-BB) and tissue inhibitors of metalloproteinase (TIMP)-1.. IL-17, TNF-alpha and IL-1beta increased VEGF secretion by synovial fibroblasts from OA patients. IL-17 and IL-1beta also increased VEGF secretion in RA and FP. Besides, IL-17 increased KGF and HGF secretions in OA, RA and FP; in OA and RA, IL-17 also increased the HB-EGF secretion and the expression of TIMP-1 as protein and mRNA. In OA patients IL-17 had an additive effect on TNF-alpha-stimulated VEGF secretion.. These results suggest that IL-17 is an in vitro stimulator of angiogenic factor release, both by its own action and by cooperating with TNF-alpha.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inducing Agents; Arthritis, Rheumatoid; Epidermal Growth Factor; Fibroblast Growth Factor 7; Fibroblasts; Fractures, Bone; Heparin-binding EGF-like Growth Factor; Hepatocyte Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-1; Interleukin-17; Middle Aged; Osteoarthritis; RNA, Messenger; Synovial Membrane; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A