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Molecules 2015, 20(5), 7586-7601;

BMP Signaling Regulates Bone Morphogenesis in Zebrafish through Promoting Osteoblast Function as Assessed by Their Nitric Oxide Production

Laboratory for Organogenesis and Regeneration, Université de Liège, GIGA-R B34, Sart Tilman, 4000 Liège, Belgium
Author to whom correspondence should be addressed.
Academic Editor: Claudio Battilocchio
Received: 28 February 2015 / Revised: 16 April 2015 / Accepted: 21 April 2015 / Published: 24 April 2015
(This article belongs to the Special Issue Nitric Oxide (NO) Release Chemistry)
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Bone morphogenetic proteins (BMPs) control many developmental and physiological processes, including skeleton formation and homeostasis. Previous studies in zebrafish revealed the crucial importance of proper BMP signaling before 48 h post-fertilization (hpf) for cartilage formation in the skull. Here, we focus on the involvement of the BMP pathway between 48 and 96 hpf in bone formation after 96 hpf. Using BMP inhibitors and the expression of a dominant-negative BMP receptor, we analyze whether the loss of BMP signaling affects osteoblastogenesis, osteoblast function and bone mineralization. To this end, we used the transgenic zebrafish line Tg(osterix:mCherry), detection of nitric oxide (NO) production, and alizarin red staining, respectively. We observed that inhibition of BMP signaling between 48 and 72 hpf led to a reduction of NO production and bone mineralization. Osteoblast maturation and chondrogenesis, on the other hand, seemed unchanged. Osteoblast function and bone formation were less affected when BMP signaling was inhibited between 72 and 96 hpf. These results suggest that for the onset of bone formation, proper BMP signaling between 48 and 72 hpf is crucial to ensure osteoblast function and ossification. Furthermore, detection of NO in developing zebrafish larvae appears as an early indicator of bone calcification activity. View Full-Text
Keywords: zebrafish; BMP; cartilage; bone; nitric oxide zebrafish; BMP; cartilage; bone; nitric oxide

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Windhausen, T.; Squifflet, S.; Renn, J.; Muller, M. BMP Signaling Regulates Bone Morphogenesis in Zebrafish through Promoting Osteoblast Function as Assessed by Their Nitric Oxide Production. Molecules 2015, 20, 7586-7601.

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