踝关节骨折后组织工程软骨类似物暴露于滑膜液血肿与软骨细胞死亡和软骨维持基因表达改变有关。

IF 2.4 2区 医学 Q2 ORTHOPEDICS
Foot & Ankle International Pub Date : 2023-09-01 Epub Date: 2023-06-17 DOI:10.1177/10711007231178829
Nicholas B Allen, Alexandra Hunter Aitchison, Kian Bagheri, Nicholas J Guardino, Bijan Abar, Samuel B Adams
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引用次数: 1

摘要

背景:骨折愈合的第一阶段包括血肿形成和促炎细胞因子和基质金属蛋白酶的募集。不幸的是,当关节内骨折时,这些炎症介质不会保留在骨折部位,而是通过滑液骨折血肿(SFFH)包裹整个关节的健康软骨。这些炎性细胞因子和基质金属蛋白酶是骨关节炎和类风湿性关节炎进展的已知因素。尽管已知SFFH的炎症成分,但很少研究SFFH对健康软骨细胞死亡和基因表达改变的影响,这些影响可能导致创伤后骨关节炎(PTOA)。方法:收集12例手术时踝关节内骨折患者的SFFH。另外,对C20A4永生化的人软骨细胞进行三维培养,以产生无支架软骨组织类似物(CTA)来模拟健康软骨。实验CTA(n = 12) 暴露于100%SFFH达3 天,洗涤并转移到完全培养基中3 天。对照CTA(n = 12) 在不暴露于SFFH的完全培养基中同时培养。随后,采集CTA并进行生化、组织学和基因表达分析。结果:CTAs暴露于踝关节SFFH达3 d显著降低软骨细胞活力34%(P = .027)。SFFH暴露后COL2A1和SOX9基因表达均显著下降(P = .012和P = .0013),而COL1A1、RUNX2和MMP13基因表达没有差异。Picrosius红染色的定量分析表明,SFFH暴露的CTAs中I型胶原沉积增加,超微结构组织较差。结论:踝关节内骨折后健康软骨组织的类器官模型暴露于SFFH导致软骨细胞活力降低,调节正常软骨细胞表型的基因表达降低,基质超微结构改变,表明向骨关节炎表型分化。临床相关性:大多数踝关节骨折不会在骨折后立即进行切开复位和内固定。事实上,这些骨折通常在几天到几周后进行治疗,以使肿胀消退。这意味着未参与骨折的健康无辜旁观者软骨在此期间暴露于SFFH。在这项研究中,SFFH导致软骨细胞活力降低和特异性基因表达改变,这可能导致骨关节炎。这些数据表明,踝关节内骨折后的早期干预可能会缓解PTOA的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exposure of Tissue-Engineered Cartilage Analogs to Synovial Fluid Hematoma After Ankle Fracture Is Associated With Chondrocyte Death and Altered Cartilage Maintenance Gene Expression.

Background: The first stage of fracture healing consists of hematoma formation with recruitment of proinflammatory cytokines and matrix metalloproteinases. Unfortunately, when there is an intra-articular fracture, these inflammatory mediators are not retained at the fracture site, but instead, envelop the healthy cartilage of the entire joint via the synovial fluid fracture hematoma (SFFH). These inflammatory cytokines and matrix metalloproteinases are known factors in the progression of osteoarthritis and rheumatoid arthritis. Despite the known inflammatory contents of the SFFH, little research has been done on the effects of the SFFH on healthy cartilage with regard to cell death and alteration in gene expression that could lead to posttraumatic osteoarthritis (PTOA).

Methods: SFFH was collected from 12 patients with intraarticular ankle fracture at the time of surgery. Separately, C20A4 immortalized human chondrocytes were 3-dimensionally cultured to create scaffold-free cartilage tissue analogs (CTAs) to simulate healthy cartilage. Experimental CTAs (n = 12) were exposed to 100% SFFH for 3 days, washed, and transferred to complete media for 3 days. Control CTAs (n = 12) were simultaneously cultured in complete medium without exposure to SFFH. Subsequently, CTAs were harvested and underwent biochemical, histological, and gene expression analysis.

Results: Exposure of CTAs to ankle SFFH for 3 days significantly decreased chondrocyte viability by 34% (P = .027). Gene expression of both COL2A1 and SOX9 were significantly decreased after exposure to SFFH (P = .012 and P = .0013 respectively), while there was no difference in COL1A1, RUNX2, and MMP13 gene expression. Quantitative analysis of Picrosirius red staining demonstrated increased collagen I deposition with poor ultrastructural organization in SFFH-exposed CTAs.

Conclusion: Exposure of an organoid model of healthy cartilage tissue to SFFH after intraarticular ankle fracture resulted in decreased chondrocyte viability, decreased expression of genes regulating normal chondrocyte phenotype, and altered matrix ultrastructure indicating differentiation toward an osteoarthritis phenotype.

Clinical relevance: The majority of ankle fracture open reduction and internal fixation does not occur immediately after fracture. In fact, typically these fractures are treated several days to weeks later in order to let the swelling subside. This means that the healthy innocent bystander cartilage not involved in the fracture is exposed to SFFH during this time. In this study, the SFFH caused decreased chondrocyte viability and specific altered gene expression that might have the potential to induce osteoarthritis. These data suggest that early intervention after intraarticular ankle fracture could possibly mitigate progression toward PTOA.

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来源期刊
Foot & Ankle International
Foot & Ankle International 医学-整形外科
CiteScore
5.60
自引率
22.20%
发文量
144
审稿时长
2 months
期刊介绍: Foot & Ankle International (FAI), in publication since 1980, is the official journal of the American Orthopaedic Foot & Ankle Society (AOFAS). This monthly medical journal emphasizes surgical and medical management as it relates to the foot and ankle with a specific focus on reconstructive, trauma, and sports-related conditions utilizing the latest technological advances. FAI offers original, clinically oriented, peer-reviewed research articles presenting new approaches to foot and ankle pathology and treatment, current case reviews, and technique tips addressing the management of complex problems. This journal is an ideal resource for highly-trained orthopaedic foot and ankle specialists and allied health care providers. The journal’s Founding Editor, Melvin H. Jahss, MD (deceased), served from 1980-1988. He was followed by Kenneth A. Johnson, MD (deceased) from 1988-1993; Lowell D. Lutter, MD (deceased) from 1993-2004; and E. Greer Richardson, MD from 2005-2007. David B. Thordarson, MD, assumed the role of Editor-in-Chief in 2008. The journal focuses on the following areas of interest: • Surgery • Wound care • Bone healing • Pain management • In-office orthotic systems • Diabetes • Sports medicine
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