The Role Of BMP-smad Signaling Pathway In The Pathogenesis Of Multiple Osteochondroma

Background:Osteochondroma,also known as exophytic osteoma,is a poorly developed cartilaginous osteophyte growing on the surface of the bone in the cartilage.Osteochondroma is divided into single osteochondroma（SO）and multiple osteochondroma（MO）.Multiple hereditary osteochondromas（MHE）is an autosomal dominant trait,Jennes et al.Found that it was characterized by high incidence of osteochondroma and bone deformity.Bovée et al.Pointed out that the clinical manifestations of Mo are often found because osteochondroma tissue compresses nearby blood vessels,nerves,tendons,bones and other tissues,resulting in pain and functional problems.So far,there has been no relevant report on the transformation of So into malignant chondrosarcoma,Mo patients are 1% 5% likely to be transformed into low-grade malignant bone tumors.The etiology and pathogenesis of Mo are complex and diverse,and there is no unified view.In recent years,the research on Mo has gradually increased.But most studies still focus on the report of a single case,A large number of clinical studies and basic research on the pathogenesis,diagnosis and treatment of Mo are still quite lacking.BMP-Smad signaling pathway plays an important role in bone development,especially cartilage development,Because bone morphogenetic protein（BMP）can stimulate the proliferation,hypertrophy and differentiation of chondrocytes,Relevant research results show that the BMP signal in the cartilage cap of osteochondroma may help to maintain the mature state of cells,It may be the key mechanism of abnormal regulation of proliferation and differentiation of chondrocytes in human osteochondroma cartilage cap.How BMP-Smad signaling pathway plays its role in the pathogenesis of osteochondroma remains to be further studied.Noggin is an important protein that inhibits BMP signal pathway.It can combine with BMP2 / 4 to form a complex,so as to block BMP signal and affect the normal development of bone.Objective:To explore the possible mechanism of BMP-Smad signaling pathway in the pathogenesis of MO,It provides a new idea for the study of MO.Methods:In this study,rabbit chondrocytes and osteochondroma were divided into:Anormal saline + rabbit chondrocytes group,Bnoggin+rabbit chondrocytes group,C normal saline + osteochondroma cells group,D noggin + osteochondroma cells group,Normal rabbit chondrocytes and osteochondroma cells were treated with equal doses of normal saline and BMP inhibitor noggin,The expressions of BMP2,Smad1 / 5/ 8,Smad4,Smad7 and Runx2 in normal rabbit chondrocytes and osteochondroma cells before and after intervention were detected by Western blot,Clarify the differences between the two.Results:According to the test results,in osteochondroma cells without any treatment,BMP2 and Runx2 increased significantly compared with normal chondrocytes,while Smad1 / 5 / 8,Smad4 and Smad7 decreased significantly compared with normal chondrocytes.Normal chondrocytes and osteochondroma cells were stimulated synchronously and equally with normal saline and noggin,The amount of BMP2 and Runx2 after noggin treatment was significantly lower than that before treatment,The amount of Smad1,Smad4,Smad5,smad8 and Smad7 increased significantly,This result is similar to that of noggin treating normal chondrocytes,There was no significant change in the normal saline treatment group.Conclusion:Smad1,Smad4,Smad5 and smad8 in osteochondroma cells observed in this study were significantly lower than those in normal chondrocytes,BMP2 is more active than normal chondrocytes,Smad7 was significantly inhibited compared with normal chondrocytes.After BMP2 was antagonized,it caused the decrease of Runx2 and the increase of Smad1,Smad4,Smad5,smad8 and Smad7.In conclusion,BMP Smad signal may be involved in the osteogenesis of osteochondroma.And in this process,the high expression of BMP2 stimulates the process of endochondral osteogenesis,The expression of Smad7 was inhibited;The lack of Smad1,Smad4,Smad5 and smad8 leads to the serious disorder of the growth plate in the perichondrium,Eventually lead to chondrocyte disorder,The proliferating chondrocytes were arranged in clusters rather than columns,which formed the osteochondroma we observed.