ZFIN ID: ZDB-PUB-190418-16
Hedgehog signaling regulates osteoblast differentiation in zebrafish larvae through modulation of autophagy
Hu, Z., Chen, B., Zhao, Q.
Impaired osteoblast differentiation may result in bone metabolic disease such as osteoporosis. It was reported recently that Hedgehog (Hh) signaling and autophagy are two important regulators of bone differentiation. In order to further dissect their relationship in bone development, we used a zebrafish larvae model to investigate how disruption of one of these signaling affects the function of another and impacts osteoblast differentiation. Our results showed that activation of Hh signaling negatively regulated autophagy. However, suppression of autophagy by knocking down atg5
expression didn't alter Hh signaling, but dramatically up-regulated the expression of osteoblast related genes and increased bone mineralization especially in den region. On the contrary, inhibition of Hh signaling pathway by cyclopamine treatment suppressed the expression of osteoblast related genes and decreased bone mineralization. In agreement with these findings, blocking Hh signaling through knock down SHH and Gli2 genes led to defective osteoblast differentiation, while promoting Hh signaling by knock down Ptch1 was beneficial to osteoblast differentiation. Our results thus support that activation of Hh signaling pathway negatively regulates autophagy and consequentially promotes osteoblast differentiation. On the contrary, induction of autophagy inhibits osteoblast differentiation. Our work revealed the mechanism underlying Hh signaling pathway regulation of bone development.