关键词: 表皮生长因子, 　骨发育, 　软骨内骨化, 　破骨细胞生成

Abstract: To determine the role of epidermal growth factor receptor (EGFR) signaling in endochondral ossification.Methods Long bones, from EGFR knockout mice (EGFR-/-),wild type (EGFR+/+) and (or) heterozygous mice (EGFR+/-) were collected and Trichrome Masson staining,in situ hybridization and tartrate-resistant acid phosphatase (TRAP) staining were used to observe endochondral ossification and recruitment of osteoclasts; Osteoclast formation was observed by addition of EGFR tyrosine kinase inhibitor AG1478 to the cultured osteoclasts from bone marrow cells. Results Due to the same phenotype of EGFR+/+ and EGFR+/-,they were regarded as EGFR+/+ in our study.EGFR deficiency caused delayed primary endochondral ossification of cartilage anlage and delayed osteoclast recruitment.The hypertrophic cartilage area in EGFR-/-mice was about 5 times longer than that in EGFR+/+ mice.There was different distribution of MMP-9 between EGFR+/+ and EGFR-/- in E16.5,but there was no difference about the quantity of MMP-9 in osteoclasts between EGFR-/- and EGFR+/+.However,inhibition of EGFR signaling with AG1478 significantly decreased osteoclast formation compared with control group with DMSO (P<0.01). Conclusion Inhibition of EGFR signaling can delay endochondral ossification,osteoclast recruitment and decrease osteoclast formation.

Key words: epidermal growth factor, bone development, endochondral ossification, osteoclast formation