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Immunohistochemical Localization of Bone Morphogenetic Proteins (BMPs) and their Receptors in Solitary and Multiple Human Osteochondromas
Authors:Araceli Cuellar  Atsuyuki Inui  Michelle A. James  Dariusz Borys  A. Hari Reddi
Affiliation:Lawrence Ellison Center for Tissue Regeneration and Repair (AC, AI, AHR), University of California Davis, Sacramento, California;Department of Orthopaedic Surgery (AC, AI, AHR), University of California Davis, Sacramento, California;Department of Pathology (DB), University of California Davis, Sacramento, California;Shriners Hospital for Children Northern California, Sacramento, California (MAJ)
Abstract:The expression of bone morphogenetic proteins (BMPs) and their cognate receptors (BMPRs) in osteochondromas has not been investigated. We determined the immunohistochemical localization and distribution of BMP-2/4, -6 and -7; BMP receptors BMPR-1A, BMPR-1B and BMPR-2; signal transducing proteins phosphorylated Smad1/5/8; and BMP antagonist noggin in the cartilaginous cap of solitary (SO) and multiple (MO) human osteochondromas and compared these with bovine growth plate and articular cartilage. The distribution and localization patterns for BMP-6, BMP-7, BMPR-1A and BMPR-2 were similar between the cartilaginous cap and the growth plate. BMP-2/4 and BMPR-1B were present throughout the growth plate. However, BMP-2/4 and phosphorylated Smad1/5/8 were mainly detected in proliferating chondrocytes of the cartilaginous cap. Also, BMPR-1B was found in hypertrophic chondrocytes of SO and proliferating chondrocytes of MO. Noggin was observed in resting chondrocytes and, to a lesser extent, in clustered proliferating chondrocytes in SO. On the other hand, noggin in MO was observed in proliferating chondrocytes. Since BMPs can stimulate proliferation and hypertrophic differentiation of chondrocytes, these findings suggest that there is an imbalance of BMP-2/4 and noggin interactions that may lead to abnormal regulation of chondrocyte proliferation and differentiation in the cartilaginous cap of human osteochondromas.
Keywords:bone morphogenetic protein   solitary osteochondroma   multiple osteochondroma   immunohistochemistry   localization   distribution
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