Abstract:
:Chondrocyte proliferation and differentiation are crucial for endochondral ossification and strictly regulated by numerous signaling molecules and transcription factors, but the hierarchical regulatory network remains to be deciphered. The present study emphasized the interplay of Activin A, Foxa, Notch and Shh signaling in the proliferation and differentiation of antler chondrocytes. We found that Activin A promoted chondrocyte proliferation and differentiation, and accelerated the transition of cell cycle from G1 into S phase along with the activation of Notch and Shh signaling whose blockage attenuated above function of Activin A. Inhibition of Notch pathway by DAPT led to a significant reduction in the expression of Shh signaling molecules, whereas addition of exogenous rShh rescued the delayed onset of chondrocyte proliferation and differentiation elicited by DAPT, indicating that Notch pathway is upstream of Shh signaling. Further analysis evidenced that DAPT attenuated the activation of Activin A on Shh signaling. Simultaneously, Foxa transcription factors were downstream targets of Shh signaling in chondrocyte differentiation. Moreover, Shh pathway played an important role in the crosstalk between Activin A-Notch signaling and Foxa. Collectively, Shh signaling may act downstream of Notch pathway to mediate the effects of Activin A on the proliferation and differentiation of antler chondrocytes through targeting Foxa.
journal_name
Bonejournal_title
Boneauthors
Ma L,Duan CC,Yang ZQ,Ding JL,Liu S,Yue ZP,Guo Bdoi
10.1016/j.bone.2019.03.036subject
Has Abstractpub_date
2019-06-01 00:00:00pages
176-188eissn
8756-3282issn
1873-2763pii
S8756-3282(19)30123-1journal_volume
123pub_type
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