Novel insights into Dhh signaling in antler chondrocyte proliferation and differentiation: Involvement of Foxa.
The desert hedgehog (Dhh) is crucial for spermatogenesis and Leydig cell differentiation, but little is known regarding its physiological function in cartilage. In this study, Dhh mRNA was abundant in antler chondrocytes, where it advanced cell proliferation concomitant with accelerated transition from the G1 to the S phase and induced elevation of the hypertrophic chondrocyte markers, Col X and Runx2. Silencing of Ptch1 resulted in appreciable Smo accumulation and enhanced rDhh stimulation of Smo, whose impediment by cyclopamine obscured the proliferative function of Dhh and alleviated its guidance of chondrocyte differentiation. Further analysis evidenced the noteworthy positive action of Smo in the bridging between Dhh and Gli transcription factors. Obstruction of Gli1 by GANT58 caused the failed stimulation of Col X and Runx2 by rDhh. Analogously, siRNA against Gli1-3 hindered chondrocyte differentiation in the context of rDhh. Simultaneously, Gli transcription factors mediated the regulation of Dhh on Foxa1, Foxa2, and Foxa3, whose knockdown impaired chondrocyte differentiation. Attenuation of Foxa antagonized the augmentation of Col X and Runx2 generated by rDhh. Collectively, Dhh signaling through its target Foxa appears to induce antler chondrocyte proliferation and differentiation.
['Ma|Li|L|', 'Duan|Cui-Cui|CC|', 'Yang|Zhan-Qing|ZQ|', 'Ding|Jun-Li|JL|', 'Liu|Shu|S|', 'Yue|Zhan-Peng|ZP|', 'Guo|Bin|B|0000-0001-5950-8974']
D000818:Animals D000999:Antlers D002356:Cartilage D002453:Cell Cycle D002454:Cell Differentiation D019902:Chondrocytes D020219:Chondrogenesis D050659:Core Binding Factor Alpha 1 Subunit D003670:Deer D051858:Forkhead Transcription Factors D053823:Hedgehog Proteins D007985:Leydig Cells D008297:Male D015398:Signal Transduction D013091:Spermatogenesis
Dhh signaling antler chondrocyte proliferation and differentiation Foxa