Lineage tracing of col10a1 cells identifies distinct progenitor populations for osteoblasts and joint cells in the regenerating fin of medaka (Oryzias latipes)

Dasyani, Manish; Tan, Wen Hui; Sundaram, Sudha; Imangali, Nurgul; Centanin, Lázaro; Wittbrodt, Joachim; Winkler, Christoph

doi:10.1016/j.ydbio.2019.07.012

Cited by 16 publications

(20 citation statements)

References 46 publications

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“…We therefore tested whether osteoblasts are the sole source for Cxcl9l required for osteoclast recruitment. As cxcl9l was up-regulated in col10a1 osteoblast progenitors as well as in premature osx -positive osteoblasts ( SI Appendix , Tables S1 and S3 ), we made use of an established osx :mCherry-NTRo line to genetically ablate premature osteoblasts using a Nitroreductase (NTRo) approach as described earlier ( 28 , 29 ) and quantified the formation of ctsk osteoclasts after Rankl induction. Metronidazole (Mtz) treatment of osx :mCherry-NTRo/ rankl :HSE: cfp / ctsk :GFP transgenic medaka at 9 dpf for 24 h resulted in an almost complete ablation of osteoblasts from the vertebral column under both Rankl− and Rankl+ conditions ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To generate osx:cxcl9l-p2a-mCherry and osx:cxcl9l-p2a-EGFP plasmids for Cxcl9l overexpression, the medaka osx promoter (16) was cloned upstream of the cxcl9l coding sequence amplified from medaka cDNA using primers cxcl9lF and cxcl9lR (SI Appendix, Table S5). For osx:cxcl9l-p2a-mCherry, the cxcl9l stop codon was replaced with p2a-mCherry amplified from plasmid col10a1:creERT2-p2a-mCherry (29). For osx:cxcl9l-p2a-EGFP, mCherry from osx:cxcl9l-p2a-mCherry was replaced with EGFP.…”

Section: Methodsmentioning

confidence: 99%

“…Transgenic lines used for nitroreductase-mediated cell ablation are described elsewhere ( 29 ). Osteoblasts were ablated by treating osx :mCherry-NTRo larvae with 8 mM metronidazole (Mtz) for 24 h at 9 dpf.…”

Section: Methodsmentioning

confidence: 99%

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Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model

Phan

Tan

Liu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Bone homeostasis requires continuous remodeling of bone matrix to maintain structural integrity. This involves extensive communication between bone-forming osteoblasts and bone-resorbing osteoclasts to orchestrate balanced progenitor cell recruitment and activation. Only a few mediators controlling progenitor activation are known to date and have been targeted for intervention of bone disorders such as osteoporosis. To identify druggable pathways, we generated a medaka (Oryzias latipes) osteoporosis model, where inducible expression of receptor-activator of nuclear factor kappa-Β ligand (Rankl) leads to ectopic formation of osteoclasts and excessive bone resorption, which can be assessed by live imaging. Here we show that upon Rankl induction, osteoblast progenitors up-regulate expression of the chemokine ligand Cxcl9l. Ectopic expression of Cxcl9l recruits mpeg1-positive macrophages to bone matrix and triggers their differentiation into osteoclasts. We also demonstrate that the chemokine receptor Cxcr3.2 is expressed in a distinct subset of macrophages in the aorta-gonad-mesonephros (AGM). Live imaging revealed that upon Rankl induction, Cxcr3.2-positive macrophages get activated, migrate to bone matrix, and differentiate into osteoclasts. Importantly, mutations in cxcr3.2 prevent macrophage recruitment and osteoclast differentiation. Furthermore, Cxcr3.2 inhibition by the chemical antagonists AMG487 and NBI-74330 also reduced osteoclast recruitment and protected bone integrity against osteoporotic insult. Our data identify a mechanism for progenitor recruitment to bone resorption sites and Cxcl9l and Cxcr3.2 as potential druggable regulators of bone homeostasis and osteoporosis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model

Phan

Tan

Liu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…In zebrafish, which are capable of complex organ regeneration, intramembranous bones of the fins and skull regenerate rapidly even after profound loss. Fin regeneration, a widely studied phenomenon of adult tissue re-growth upon fin resection (amputation) is driven by a tissue referred to as the blastema, which arises from mature cells undergoing dedifferentiation and a pool of reserved progenitor cells (1–3). The fin regenerate, being composed of different tissues (epidermis, bone, mesenchyme, blood vessels, nerves) is a structure of modest complexity which, together with the fact that it is easy to access and monitor, makes it a valuable system to study bone formation, wound healing, and cell metabolism.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid Treatment Leads to Aberrant Ion and Macromolecular Transport in Regenerating Zebrafish Fins

et al. 2019

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Long-term glucocorticoid administration in patients undergoing immunosuppressive and anti-inflammatory treatment is accompanied by impaired bone formation and increased fracture risk. Furthermore, glucocorticoid treatment can lead to impaired wound healing and altered cell metabolism. Recently, we showed that exposure of zebrafish to the glucocorticoid prednisolone during fin regeneration impacts negatively on the length, bone formation, and osteoblast function of the regenerate. The underlying cellular and molecular mechanisms of impairment, however, remain incompletely understood. In order to further elucidate the anti-regenerative effects of continued glucocorticoid exposure on fin tissues, we performed proteome profiling of fin regenerates undergoing prednisolone treatment, in addition to profiling of homeostatic fin tissue and fins undergoing undisturbed regeneration. By using LC-MS (liquid chromatography-mass spectrometry) we identified more than 6,000 proteins across all tissue samples. In agreement with previous reports, fin amputation induces changes in chromatin structure and extracellular matrix (ECM) composition within the tissue. Notably, prednisolone treatment leads to impaired expression of selected ECM components in the fin regenerate. Moreover, the function of ion transporting ATPases and other proteins involved in macromolecule and vesicular transport mechanisms of the cell appears to be altered by prednisolone treatment. In particular, acidification of membrane-enclosed organelles such as lysosomes is inhibited. Taken together, our data indicate that continued synthetic glucocorticoid exposure in zebrafish deteriorates cellular trafficking processes in the regenerating fin, which interferes with appropriate tissue restoration upon injury.

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“…NTR/Mtz system has been used to tease out the functions of specific cell types in a complex process of organ regeneration in zebrafish, including the heart (Curado et al, 2007;Wang et al, 2013;Zhang et al, 2013), fin (Petrie et al, 2014), pancreatic β-cells (Pisharath et al, 2007), bone (Willems et al, 2012) and RPE regeneration (Hanovice et al, 2019). This system is also applicable to medaka, demonstrated by accessing regeneration capacity using NTR/Mtz mediated genetic ablation of the pancreatic β-cell population (Otsuka and Takeda, 2017), osteoblasts (Willems et al, 2012), and bone progenitor cells (Dasyani et al, 2019) in fin regeneration.…”

Section: Injury Modelsmentioning

confidence: 99%

Comparative Study in Zebrafish and Medaka Unravels the Mechanisms of Tissue Regeneration

2022

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Tissue regeneration has been in the spotlight of research for its fascinating nature and potential applications in human diseases. The trait of regenerative capacity occurs diversely across species and tissue contexts, while it seems to decline over evolution. Organisms with variable regenerative capacity are usually distinct in phylogeny, anatomy, and physiology. This phenomenon hinders the feasibility of studying tissue regeneration by directly comparing regenerative with non-regenerative animals, such as zebrafish (Danio rerio) and mice (Mus musculus). Medaka (Oryzias latipes) is a fish model with a complete reference genome and shares a common ancestor with zebrafish approximately 110–200 million years ago (compared to 650 million years with mice). Medaka shares similar features with zebrafish, including size, diet, organ system, gross anatomy, and living environment. However, while zebrafish regenerate almost every organ upon experimental injury, medaka shows uneven regenerative capacity. Their common and distinct biological features make them a unique platform for reciprocal analyses to understand the mechanisms of tissue regeneration. Here we summarize current knowledge about tissue regeneration in these fish models in terms of injured tissues, repairing mechanisms, available materials, and established technologies. We further highlight the concept of inter-species and inter-organ comparisons, which may reveal mechanistic insights and hint at therapeutic strategies for human diseases.

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Lineage tracing of col10a1 cells identifies distinct progenitor populations for osteoblasts and joint cells in the regenerating fin of medaka (Oryzias latipes)

Cited by 16 publications

References 46 publications

Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model

Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model

Glucocorticoid Treatment Leads to Aberrant Ion and Macromolecular Transport in Regenerating Zebrafish Fins

Comparative Study in Zebrafish and Medaka Unravels the Mechanisms of Tissue Regeneration

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