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在单细胞水平上对颞下颌关节髁突软骨过载诱导终末分化的机制性见解

Mechanistic Insights Into Overloading-Induced Terminal Differentiation of TMJ Condylar Cartilage at the Single Cell Level.

作者信息

Zhou Dian, Jiang Yiling, Li Yingcui, Zeng Huanyu, Li Xinchun, He Yufang, Wang Xin, Liang Yiteng, Parizek Vojtech, Liu Ousheng, Tang Zhangui, Zhou Yueying

机构信息

Hunan Key Laboratory of Oral Health Research Hunan 3D Printing Engineering Research Center of Oral Care Hunan Clinical Research Center of Oral Major Diseases and Oral Health Xiangya Stomatological Hospital Xiangya School of Stomatology Central South University Changsha China.

Department of Biology University of Hartford West Hartford Connecticut USA.

出版信息

Smart Med. 2025 Jul 30;4(3):e70011. doi: 10.1002/smmd.70011. eCollection 2025 Sep.

DOI:10.1002/smmd.70011
PMID:40837199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12362756/
Abstract

The incidence of temporomandibular joint (TMJ) degeneration has been steadily increasing, with overloading identified as a major risk factor. This condition often leads to condylar cartilage degeneration, significantly affecting patients' quality of life; however, the molecular mechanisms underlying this process remain poorly understood, and effective treatments are still lacking. We utilized single-nucleus RNA sequencing to analyze the condylar cartilage in an overloading mouse model. This approach enabled the identification of 11 distinct cell types within the condylar chondrocytes. Through the application of pseudotime trajectory Analysis and cellchat analyses, we identified the key gene Acvr1b and its associated signaling pathway, which are crucial for regulating the terminal differentiation of condylar chondrocytes. This study utilized single-nucleus RNA sequencing and in vitro validation to investigate the role of Acvr1b in TMJ cartilage degeneration under overloading stress. Our findings reveal key pathways involved in chondrocyte differentiation, providing a theoretical basis for the development of targeted therapeutic interventions.

摘要

颞下颌关节(TMJ)退变的发生率一直在稳步上升,超负荷被确定为主要风险因素。这种情况常导致髁突软骨退变,严重影响患者的生活质量;然而,这一过程背后的分子机制仍知之甚少,且仍缺乏有效的治疗方法。我们利用单核RNA测序分析了超负荷小鼠模型中的髁突软骨。这种方法能够在髁突软骨细胞中鉴定出11种不同的细胞类型。通过应用伪时间轨迹分析和细胞间通讯分析,我们鉴定出关键基因Acvr1b及其相关信号通路,它们对于调节髁突软骨细胞的终末分化至关重要。本研究利用单核RNA测序和体外验证来研究Acvr1b在超负荷应激下TMJ软骨退变中的作用。我们的研究结果揭示了软骨细胞分化所涉及的关键通路,为开发靶向治疗干预措施提供了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/f9d91d851da2/SMMD-4-e70011-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/c63ca2a31cce/SMMD-4-e70011-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/5b23439ff0dc/SMMD-4-e70011-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/a993d420a59d/SMMD-4-e70011-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/9781fe86240a/SMMD-4-e70011-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/5596dc227da1/SMMD-4-e70011-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/f9d91d851da2/SMMD-4-e70011-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/c63ca2a31cce/SMMD-4-e70011-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/5b23439ff0dc/SMMD-4-e70011-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/a993d420a59d/SMMD-4-e70011-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/9781fe86240a/SMMD-4-e70011-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/5596dc227da1/SMMD-4-e70011-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8387/12362756/f9d91d851da2/SMMD-4-e70011-g001.jpg

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本文引用的文献

1
The effect of ACVR1B/TGFBR1/ACVR1C signaling inhibition on oocyte and granulosa cell development during in vitro growth culture.ACVR1B/TGFBR1/ACVR1C 信号通路抑制对体外生长培养过程中卵母细胞和颗粒细胞发育的影响。
J Reprod Dev. 2023 Oct 20;69(5):270-278. doi: 10.1262/jrd.2023-041. Epub 2023 Sep 19.
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Potential pathological and molecular mechanisms of temporomandibular joint osteoarthritis.颞下颌关节骨关节炎的潜在病理及分子机制
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PTHrP promotes subchondral bone formation in TMJ-OA.
PTHrP 促进 TMJ-OA 软骨下骨形成。
Int J Oral Sci. 2022 Jul 19;14(1):37. doi: 10.1038/s41368-022-00189-x.
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Lack of and synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration.缺乏 和 协同刺激肌纤维肥大,并加速肌肉再生。
Elife. 2022 Mar 24;11:e77610. doi: 10.7554/eLife.77610.
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Overloading stress-induced progressive degeneration and self-repair in condylar cartilage.髁突软骨过度负荷应激诱导的进行性退变和自我修复。
Ann N Y Acad Sci. 2021 Nov;1503(1):72-87. doi: 10.1111/nyas.14606. Epub 2021 May 7.
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Pathological mechanism of chondrocytes and the surrounding environment during osteoarthritis of temporomandibular joint.颞下颌关节骨关节炎中软骨细胞及周围环境的病理机制。
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Inference and analysis of cell-cell communication using CellChat.使用 CellChat 进行细胞间通讯的推断和分析。
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Prevalence of clinical signs and pain symptoms of temporomandibular disorders and associated factors in adult Finns.成人芬兰人群颞下颌关节紊乱的临床体征和疼痛症状的流行情况及相关因素。
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