Molecular Physiology of the Hypocalcemic Action of Fibroblast Growth Factor 23 in Zebrafish (Danio rerio)

Lin, Cheng Huang; Hu, Huei-Jyun; Hwang, Pung‐Pung

doi:10.1210/en.2016-1883

Cited by 7 publications

(6 citation statements)

References 46 publications

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“…fgf23 expression is stimulated by ambient water with a high calcium level. Overexpression of fgf23 in zebrafish lead to inhibition of calcium uptake by downregulating the expression of the epithelium calcium channel (ECaC) suggesting that FGF23 functions as a hypocalcemic hormone ( 283 ). Besides, a previous study also using zebrafish, reported that FGF23 regulates phosphate homeostasis ( 284 ).…”

Section: Osteokinesmentioning

confidence: 99%

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

et al. 2023

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Control of tissue metabolism and growth involves interactions between organs, tissues, and cell types, mediated by cytokines or direct communication through cellular exchanges. Indeed, over the past decades, many peptides produced by adipose tissue, skeletal muscle and bone named adipokines, myokines and osteokines respectively, have been identified in mammals playing key roles in organ/tissue development and function. Some of them are released into the circulation acting as classical hormones, but they can also act locally showing autocrine/paracrine effects. In recent years, some of these cytokines have been identified in fish models of biomedical or agronomic interest. In this review, we will present their state of the art focusing on local actions and inter-tissue effects. Adipokines reported in fish adipocytes include adiponectin and leptin among others. We will focus on their structure characteristics, gene expression, receptors, and effects, in the adipose tissue itself, mainly regulating cell differentiation and metabolism, but in muscle and bone as target tissues too. Moreover, lipid metabolites, named lipokines, can also act as signaling molecules regulating metabolic homeostasis. Regarding myokines, the best documented in fish are myostatin and the insulin-like growth factors. This review summarizes their characteristics at a molecular level, and describes both, autocrine effects and interactions with adipose tissue and bone. Nonetheless, our understanding of the functions and mechanisms of action of many of these cytokines is still largely incomplete in fish, especially concerning osteokines (i.e., osteocalcin), whose potential cross talking roles remain to be elucidated. Furthermore, by using selective breeding or genetic tools, the formation of a specific tissue can be altered, highlighting the consequences on other tissues, and allowing the identification of communication signals. The specific effects of identified cytokines validated through in vitro models or in vivo trials will be described. Moreover, future scientific fronts (i.e., exosomes) and tools (i.e., co-cultures, organoids) for a better understanding of inter-organ crosstalk in fish will also be presented. As a final consideration, further identification of molecules involved in inter-tissue communication will open new avenues of knowledge in the control of fish homeostasis, as well as possible strategies to be applied in aquaculture or biomedicine.

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Section: Osteokinesmentioning

confidence: 99%

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

et al. 2023

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“…Two other genes caught our attention: the stanniocalcin 1-like (stc1l) gene and the osteocrin (ostn) gene, which both were strongly upregulated in P1, but downregulated in P2 (Figures 2B and 3). These genes play a role in calcium homeostasis [73] and skeletal development [74,75], respectively, and both are expressed specifically, but not exclusively in the corpuscles of Stannius. Whether this means that the P1 population contains corpuscule of Stannius cells, which would express low amounts of sp7, or whether these genes are also expressed transiently in osteoblast precursor cells will need to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

The Osteoblast Transcriptome in Developing Zebrafish Reveals Key Roles for Extracellular Matrix Proteins Col10a1a and Fbln1 in Skeletal Development and Homeostasis

Raman,

Antony,

Nivelle

et al. 2024

Biomolecules

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Zebrafish are now widely used to study skeletal development and bone-related diseases. To that end, understanding osteoblast differentiation and function, the expression of essential transcription factors, signaling molecules, and extracellular matrix proteins is crucial. We isolated Sp7-expressing osteoblasts from 4-day-old larvae using a fluorescent reporter. We identified two distinct subpopulations and characterized their specific transcriptome as well as their structural, regulatory, and signaling profile. Based on their differential expression in these subpopulations, we generated mutants for the extracellular matrix protein genes col10a1a and fbln1 to study their functions. The col10a1a−/− mutant larvae display reduced chondrocranium size and decreased bone mineralization, while in adults a reduced vertebral thickness and tissue mineral density, and fusion of the caudal fin vertebrae were observed. In contrast, fbln1−/− mutants showed an increased mineralization of cranial elements and a reduced ceratohyal angle in larvae, while in adults a significantly increased vertebral centra thickness, length, volume, surface area, and tissue mineral density was observed. In addition, absence of the opercle specifically on the right side was observed. Transcriptomic analysis reveals up-regulation of genes involved in collagen biosynthesis and down-regulation of Fgf8 signaling in fbln1−/− mutants. Taken together, our results highlight the importance of bone extracellular matrix protein genes col10a1a and fbln1 in skeletal development and homeostasis.

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“…5A). Stc1a is an anti-hypercalcemic hormone triggered by high environmental calcium through activation of the Calcium-Sensing Receptor (CaSR) 33,[76][77][78] . Stc1a reduces calcium uptake to maintain physiologically safe levels by inhibiting proliferation of NaR cells and suppressing trpv6 expression 42,45 .…”

Section: Endocrine Suppression Of Nar Ionocyte Expansion In Sox10 Mut...mentioning

confidence: 99%

“…5C-D) or also to a percell increase in transcription is not yet clear. Previous studies have shown that high external calcium upregulates stc1a transcription at least in part via the Calcium-Sensing Receptor (CaSR), which is also expressed in the CS 77 . Aberrant activity of CaSR in the absence of sox10+ lineage cells could therefore potentially boost stc1a transcription.…”

Section: Sox10 Drives Bone Mineralization Indirectly Through Interact...mentioning

confidence: 99%

Sox10 is required for systemic initiation of bone mineralization

Gjorcheska,

Paudel,

McLeod

et al. 2024

Preprint

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Heterozygous variants in the gene encoding the SOX10 transcription factor cause congenital syndromes affecting pigmentation, digestion, hearing, and neural function. Most of these symptoms are attributable to failed differentiation and loss of neural crest cells. Extensive research on mouse and zebrafish models has confirmed that Sox10 is essential for most non-skeletal crest derivatives, but seemingly dispensable for skeletal development. We challenge that concept here by revealing a novel requirement for Sox10 in skeletal mineralization. Neither neural crest- nor mesoderm-derived bones initiate mineralization on time in zebrafish sox10 mutants, despite normal osteoblast differentiation and matrix production. We show that mutants are deficient in the ionocyte subpopulation tasked with taking up calcium from the environment through the Trpv6 epithelial calcium channel, leading to a severe calcium deficit that explains the lack of mineralization. As these ionocytes do not derive from a sox10+ lineage, we hypothesized that the primary defect instead resides in a separate organ that regulates ionocyte numbers or calcium uptake at a systemic level. Screening of the endocrine hormones known to regulate calcium homeostasis in adult vertebrates revealed significantly elevated levels of stanniocalcin (Stc1a), an anti-hypercalcemic hormone, in larval sox10 mutants. Previous studies demonstrated that Stc1a inhibits calcium uptake in fish by repressing trpv6 expression and blocking proliferation of Trpv6+ ionocytes. Our epistasis assays indicate that excess Stc1a is the proximate cause of the calcium deficit in sox10 mutants. Lineage tracing shows that the pronephros-derived glands that synthesize Stc1a interact with sox10+ neural crest-derived cells, and that the latter are missing in mutants. We conclude that a subpopulation of Sox10+ neural crest non-cell-autonomously limit Stc1a production to allow the inaugural wave of calcium uptake necessary for the initiation of bone mineralization.

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Molecular Physiology of the Hypocalcemic Action of Fibroblast Growth Factor 23 in Zebrafish (Danio rerio)

Cited by 7 publications

References 46 publications

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

The Osteoblast Transcriptome in Developing Zebrafish Reveals Key Roles for Extracellular Matrix Proteins Col10a1a and Fbln1 in Skeletal Development and Homeostasis

Sox10 is required for systemic initiation of bone mineralization

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