Regeneration of Jaw Joint Cartilage in Adult Zebrafish.

Regeneration of Jaw Joint Cartilage in Adult Zebrafish.
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DOI:
10.3389/fcell.2021.777787
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发表时间:
2021
影响因子:
5.5
通讯作者:
Crump JG
Crump JG
中科院分区:
生物学2区
文献类型:
--
作者:
Smeeton J;Natarajan N;Anderson T;Tseng KC;Fabian P;Crump JG

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哺乳动物关节软骨的固有修复能力差可能导致全球关节炎的高发病率。成年斑马鱼可以再生许多在哺乳动物中表现出有限或没有愈合能力的结构,包括颌骨。为了测试斑马鱼是否也可以再生受损的关节,我们开发了一种手术损伤模型,其中通过切断主要的下颌关节韧带,即下颌骨间韧带(IOM),使斑马鱼的下颌关节不稳定。在1岁的鱼的IOM韧带的单侧横切导致在最初的减少下颌关节软骨的14天,与完全再生的关节软骨的28天。关节软骨再生涉及关节软骨细胞重新进入细胞周期和sox10的表达上调,sox10是胚胎中软骨细胞发育的标志物,在成人中仅限于关节软骨细胞的一个子集。这些sox10表达软骨细胞的基因消融表明,它们对关节软骨再生至关重要。为了揭示关节再生过程中新软骨细胞的潜在来源,我们对未受伤的成人颌关节进行了单细胞RNA测序,并鉴定了多种骨骼、结缔组织和成纤维细胞亚型。特别是,我们发现了一个关节特异性骨膜人口表达coch和grem1a,与颌骨关节软骨细胞标记的grem1a表达在再生过程中。我们的研究结果证明了斑马鱼再生成人关节软骨的能力,并确定了可以测试其在再生反应中作用的候选细胞类型。
The poor intrinsic repair capacity of mammalian joint cartilage likely contributes to the high incidence of arthritis worldwide. Adult zebrafish can regenerate many structures that show limited or no healing capacity in mammals, including the jawbone. To test whether zebrafish can also regenerate damaged joints, we developed a surgical injury model in which the zebrafish jaw joint is destabilized via transection of the major jaw joint ligament, the interopercular–mandibular (IOM). Unilateral transection of the IOM ligament in 1-year-old fish resulted in an initial reduction of jaw joint cartilage by 14 days, with full regeneration of joint cartilage by 28 days. Joint cartilage regeneration involves the re-entry of articular chondrocytes into the cell cycle and the upregulated expression of sox10, a marker of developing chondrocytes in the embryo that becomes restricted to a subset of joint chondrocytes in adults. Genetic ablation of these sox10-expressing chondrocytes shows that they are essential for joint cartilage regeneration. To uncover the potential source of new chondrocytes during joint regeneration, we performed single-cell RNA sequencing of the uninjured adult jaw joint and identified multiple skeletal, connective tissue, and fibroblast subtypes. In particular, we uncovered a joint-specific periosteal population expressing coch and grem1a, with the jaw joint chondrocytes marked by grem1a expression during regeneration. Our findings demonstrate the capacity of zebrafish to regenerate adult joint cartilage and identify candidate cell types that can be tested for their roles in regenerative response.
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