Bone morphogenetic protein-7 (BMP-7) is a growth and differentiation factor and belongs to the TGF-beta superfamily of proteins. Previous studies have shown an abundant expression of BMP-7 in the developing intestine and an association with a perturbed BMP/SMAD downstream signaling leading to a malignant phenotype and inflammation in the gut. In the present study, we have evaluated the effect of systemically administered recombinant human BMP-7 against trinitrobenzenesulfonic (TNBS) acid induced inflammatory bowel disease (IBD) in rats. The TNBS administered rats treated with BMP-7 have developed much less severe form of colitis based on macroscopic and histological scoring when administered 1.5 h before or 24 h after colitis induction. Bioavailability studies in healthy rats have revealed that significant portion (3.6%) of i.v. administered BMP-7 is targeted for BMP-7 receptors in the stomach and ileum, respectively, suggesting its availability to target tissue upon administration. Immunohistochemical and RT-PCR analyses have shown elevated expression of pro-inflammatory (IL-6, TNF-beta, ICAM-1) and pro-fibrogenic (TGF-beta) cytokines, and BMP-7 treatment significantly reduced their expression in the intestine; among which the suppression of IL-6 appeared to be the most important. Taken together, the results of this study suggest that BMP-7 plays an important role in the regulation of anti-inflammatory response in the adult gut tissue.
Bone-and cartilage-derived morphogenetic proteins (BMPs and CDMPs), which are TGF β superfamily members, are growth and differentiation factors that have been recently isolated, cloned and biologically characterized. They are important regulators of key events in the processes of bone formation during embryogenesis, postnatal growth, remodelling and regeneration of the skeleton. In the present study, we used immunohistochemical methods to investigate the distribution of BMP-2, -3, -5, -6, -7 and CDMP-1, -2, -3 in human osteophytes (abnormal bony outgrowths) isolated from osteoarthritic hip and knee joints from patients undergoing total joint replacement surgery. All osteophytes consisted of three different areas of active bone formation: (1) endochondral bone formation within cartilage residues; (2) intramembranous bone formation within the fibrous tissue cover and (3) bone formation within bone marrow spaces. The immunohistochemistry of certain BMPs and CDMPs in each of these three different bone formation sites was determined. The results indicate that each BMP has a distinct pattern of distribution. Immunoreactivity for BMP-2 was observed in fibrous tissue matrix as well as in osteoblasts; BMP-3 was mainly present in osteoblasts; BMP-6 was restricted to young osteocytes and bone matrix; BMP-7 was observed in hypertrophic chondrocytes, osteoblasts and young osteocytes of both endochondral and intramembranous bone formation sites. CDMP-1, -2 and -3 were strongly expressed in all cartilage cells. Surprisingly, BMP-3 and -6 were found in osteoclasts at the sites of bone resorption. Since a similar distribution pattern of bone morphogenetic proteins was observed during embryonal bone development, it is suggested that osteophyte formation is regulated by the same molecular mechanism as normal bone during embryogenesis.
The variations of the common carotid artery, as well as of the external and internal carotid arteries, are described. During anatomic dissection on adult cadavers, we investigated the variability of appearance of 40 carotid arterial systems. Special consideration was given to the topographic relations such as the level of the bifurcation of the common carotid artery, the relationship between the external and internal carotid arteries, and the origin of the great collateral branches. Special attention was paid to the origin of the superior thyroid artery. In this article the practical importance of these variations is stressed.
The variations of the common carotid artery, as well as of the external and internal carotid arteries, are described. During anatomic dissection on adult cadavers, we investigated the variability of appearance of 40 carotid arterial systems. Special consideration was given to the topographic relations such as the level of the bifurcation of the common carotid artery, the relationship between the external and internal carotid arteries, and the origin of the great collateral branches. Special attention was paid to the origin of the superior thyroid artery. In this article the practical importance of these variations is stressed.
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