Axin2-lineage cells contribute to neonatal tendon regeneration.

IF 2.8 4区医学 Q3 CELL BIOLOGY Connective Tissue Research Pub Date : 2022-09-01 DOI:10.1080/03008207.2022.2036732

B Walia, T M Li, G Crosio, A M Montero, A H Huang

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引用次数: 5

Abstract

Purpose: Tendon injuries are a challenging clinical problem with few treatment options. Identifying the molecular regulators of tendon is required for the development of new therapies. While the Wnt pathway is critical for the maintenance and differentiation of many tissues, the role of Wnt signaling in tendon cell biology remains largely unexplored.

Methods: The effects of Wnt activation were tested in vitro using neonatal tendon-derived cells cultured in 2D and 3D conditions. The inducible Axin2CreERT2 was then used to label Axin2+ cells in vivo and cells were traced during neonatal tendon regeneration.

Results: We showed that activation of Wnt signaling results in proliferation of neonatal tendon cells. While tendon marker expression was inhibited by Wnt activation under 2D conditions, Scx expression was not affected under 3D uniaxial tension, suggesting that the microenvironment contextualizes tendon cell response to Wnt signaling. Using an in vivo model of neonatal tendon regeneration, we further showed that Wnt signaling cells comprise a subpopulation of tenocyte and epitenon cells that proliferate after injury and are recruited during regeneration.

Discussion: Collectively, these studies suggest that Wnt signaling may play a role in tendon cell proliferation, differentiation, and regeneration.

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axin2系细胞有助于新生儿肌腱再生。

目的:肌腱损伤是一个具有挑战性的临床问题，治疗方案很少。确定肌腱的分子调节因子是开发新疗法所必需的。虽然Wnt通路对许多组织的维持和分化至关重要，但Wnt信号在肌腱细胞生物学中的作用仍未得到充分研究。方法:利用新生肌腱源性细胞，在体外二维和三维培养条件下检测Wnt的激活作用。然后用可诱导的Axin2CreERT2在体内标记Axin2+细胞，并在新生儿肌腱再生过程中追踪细胞。结果:我们发现Wnt信号的激活导致新生儿肌腱细胞的增殖。在二维条件下，Wnt激活会抑制肌腱标记物的表达，而在三维单轴张力条件下，Scx的表达不受影响，这表明微环境影响了肌腱细胞对Wnt信号的反应。通过新生儿肌腱再生的体内模型，研究人员进一步发现Wnt信号细胞由肌腱细胞和上皮细胞组成，这些细胞在损伤后增殖，并在再生过程中被招募。讨论:总的来说，这些研究表明Wnt信号可能在肌腱细胞增殖、分化和再生中发挥作用。

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来源期刊

Connective Tissue Research 生物-细胞生物学

CiteScore

6.60

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.