Responding to ACL Injury and its Treatments: Comparative Gene Expression between Articular Cartilage and Synovium.
Responding to ACL Injury and its Treatments: Comparative Gene Expression between Articular Cartilage and Synovium.
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DOI：
10.3390/bioengineering10050527
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发表时间：
2023-04-26
期刊：
影响因子：
--
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中科院分区：
文献类型：
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软骨和滑膜之间的关系是骨关节炎研究中快速发展的领域。然而，据我们所知，这两种组织之间的基因表达的关系尚未在中期疾病发展中探索。目前的研究比较了创伤后骨关节炎诱导和多种手术治疗方式后一年的大型动物模型中这两种组织的转录组。36头尤卡坦小型猪接受了前交叉韧带横断术。受试者被随机分配到无进一步干预、韧带重建或用细胞外基质（ECM）支架增强的韧带修复组，然后在收获后52周对关节软骨和滑膜进行RNA测序。12个完整的对侧膝关节作为对照。在所有治疗方式中，转录组的主要差异是，与滑膜相比，关节软骨具有更大的免疫激活相关基因上调-一旦软骨和滑膜之间的基线差异被调整。与关节软骨相比，滑膜中与Wnt信号传导相关的基因上调更大。在调整韧带重建后观察到的软骨和滑膜之间的表达差异后，相对于滑膜，用ECM支架进行的韧带修复上调了与软骨中的离子稳态、组织重塑和胶原蛋白降解相关的途径。这些发现暗示了创伤后骨关节炎中期发展中软骨内的炎症通路，与手术治疗无关。此外，ECM支架的使用可以通过优先激活软骨内的离子稳态和组织重塑途径来发挥优于金标准重建的软骨保护作用。
The relationship between cartilage and synovium is a rapidly growing area of osteoarthritis research. However, to the best of our knowledge, the relationships in gene expression between these two tissues have not been explored in mid-stage disease development. The current study compared the transcriptomes of these two tissues in a large animal model one year following posttraumatic osteoarthritis induction and multiple surgical treatment modalities. Thirty-six Yucatan minipigs underwent transection of the anterior cruciate ligament. Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair augmented with an extracellular matrix (ECM) scaffold, followed by RNA sequencing of the articular cartilage and synovium at 52 weeks after harvest. Twelve intact contralateral knees served as controls. Across all treatment modalities, the primary difference in the transcriptomes was that the articular cartilage had greater upregulation of genes related to immune activation compared to the synovium—once baseline differences between cartilage and synovium were adjusted for. Oppositely, synovium featured greater upregulation of genes related to Wnt signaling compared to articular cartilage. After adjusting for expression differences between cartilage and synovium seen following ligament reconstruction, ligament repair with an ECM scaffold upregulated pathways related to ion homeostasis, tissue remodeling, and collagen catabolism in cartilage relative to synovium. These findings implicate inflammatory pathways within cartilage in the mid-stage development of posttraumatic osteoarthritis, independent of surgical treatment. Moreover, use of an ECM scaffold may exert a chondroprotective effect over gold-standard reconstruction through preferentially activating ion homeostatic and tissue remodeling pathways within cartilage.
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影响因子：
5.1
作者：
Katsoula G;Kreitmaier P;Zeggini E
通讯作者：
Zeggini E
DOI：
10.1177/0363546521989265
发表时间：
2021-03
期刊：
The American journal of sports medicine
影响因子：
--
作者：
Karamchedu NP;Murray MM;Sieker JT;Proffen BL;Portilla G;Costa MQ;Molino J;Fleming BC
通讯作者：
Fleming BC
影响因子：
12.7
作者：
Findlay, David M.;Kuliwaba, Julia S.
通讯作者：
Kuliwaba, Julia S.
影响因子：
4.6
作者：
Chou, Ching-Heng;Jain, Vaibhav;Kraus, Virginia B.
通讯作者：
Kraus, Virginia B.
影响因子：
3.9
作者：
Klein-Wieringa, Inge R.;de lange-Brokaar, Badelog J. E.;Ioan-Facsinay, Andreea
通讯作者：
Ioan-Facsinay, Andreea