Novel insights into Dhh signaling in antler chondrocyte proliferation and differentiation: Involvement of Foxa
| Autor: | Cui-Cui Duan, Zhan-Qing Yang, Shu Liu, Bin Guo, Li Ma, Jun-Li Ding, Zhan-Peng Yue |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Cyclopamine Physiology Clinical Biochemistry Context (language use) Antlers Core Binding Factor Alpha 1 Subunit Chondrocyte 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Chondrocytes GLI1 medicine Animals Hedgehog Proteins Spermatogenesis Transcription factor Desert hedgehog biology Deer Cell Cycle Leydig Cells Leydig cell differentiation Cell Differentiation Forkhead Transcription Factors Cell Biology Cell biology RUNX2 030104 developmental biology medicine.anatomical_structure Cartilage chemistry 030220 oncology & carcinogenesis biology.protein Chondrogenesis Signal Transduction |
| Zdroj: | Journal of cellular physiologyREFERENCES. 235(9) |
| ISSN: | 1097-4652 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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