title: Epithelial-mesenchymal transition and mesenchymal-epithelial transition response during differentiation of growth-plate chondrocytes in endochondral ossification.
abstract: For linear longitudinal bone elongation, the stem-like progenitor chondrocytes distributed in resting zone (RZ) of growth plate have a capacity to differentiate towards the spindle chondrocytes in proliferative zone (PZ), then towards the columnar and tightly adjacent chondrocytes in hypertrophic zone (HZ). We hypothesized this process of endochondral ossification with cells morphological change was occurred along with the inter-conversion between epithelial to mesenchymal cell types. Consistent with this hypothesis, our study demonstrated the chondrocytes highly expressed mesenchymal-like biomarkers and loss of epithelial surface markers in PZ, while converse in RZ and HZ of the growth plate in mice distal tibia in vivo. To further determine these process and correlation regulatory pathway, the 4-week old male and female mice were treated with estradiol cypionate or oxandrolone, then investigated the response of epithelial- and mesenchymal biomarkers, and demonstrated that estrogen blocked the EMT process from RZ to PZ while androgen promoted MET from PZ to HZ. Our observations supported the hypotheses that the growth plate firstly go through EMT from RZ to PZ, then MET process from PZ to HZ during the epiphyseal fusion. Our results could interpret the different roles of estrogen and androgen in growth plate cartilage when endochondral ossification.
authors.affiliation: Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200040, People's Republic of China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Divisions of Cancer Biology, University of Hawaii Cancer Center, University of Hawaii Honolulu, HI, 96813, USA.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Oncology, Jinan Central Hospital Affiliated to Shandong University Jinan 250013, Shandong, People's Republic of China ; Department of Radiation Oncology, Shandong Cancer Hospital and Institute Jinan 250117, Shandong, People's Republic of China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200040, People's Republic of China.
authors.forename: Pin
authors.initials: P
authors.lastname: Li
keywords: EMT; Growth plate; MET; androgen; cartilage; estrogen