成纤维细胞活化蛋白
成纤维细胞
肩膀
医学
阿尔法(金融)
肩袖
肌腱
免疫组织化学
纤维连接蛋白
病理
核医学
外科
细胞外基质
内科学
生物
细胞培养
癌症
细胞生物学
患者满意度
遗传学
结构效度
作者
Xueying Zhang,Daoyun Chen,John W. Babich,Samuel J. E. Green,Xiang‐Hua Deng,Scott A. Rodeo
标识
DOI:10.2106/jbjs.20.00831
摘要
Rotator cuff repair site failure is a well-established clinical concern. Tendon-to-bone healing is initiated by inflammatory mediators followed by matrix synthesis by fibroblasts. The kinetics of fibroblast accumulation and activity are currently poorly understood.Ninety-six mice underwent supraspinatus tendon repair. Six were used for imaging using a novel 68Gallium (Ga)-labeled fibroblast activation protein alpha (FAP-α) inhibitor and positron emission tomography-computed tomography (PET/CT) at days 0 (before surgery), 3, 7, 14, and 28. Sixty-eight animals were divided into 4 groups to be evaluated at 3, 7, 14, or 28 days. Twenty-two native shoulders from mice without surgery were used as the control group (intact tendon). Six animals from each group were used for histological analysis; 6 from each group were used for evaluation of fibroblastic response-related gene expression; and 10 mice each from the intact, 14-day, and 28-day groups were used for biomechanical testing.There was minimal localization of 68Ga-labeled FAP-α inhibitor in the shoulders at day 0 (before surgery). There was significantly increased uptake in the shoulders with surgery compared with the contralateral sides without surgery at 3, 7, and 14 days. 68Ga-labeled FAP-α inhibitor uptake in the surgically treated shoulders increased gradually and peaked at 14 days followed by a decrease at 28 days. Gene expression for smooth muscle alpha (α)-2 (acta2), FAP-α, and fibronectin increased postsurgery followed by a drop at 28 days. Immunohistochemical analysis showed that FAP-α-positive cell density followed a similar temporal trend, peaking at 14 days. All trends matched closely with the PET/CT results. Biomechanical testing demonstrated a gradual increase in failure load during the healing process.68Ga-labeled FAP-α inhibitor PET/CT allows facile, high-contrast in vivo 3-dimensional imaging of fibroblastic activity in a mouse rotator cuff repair model.Noninvasive imaging of activated fibroblasts using labeled radiotracers may be a valuable tool to follow the progression of healing at the bone-tendon interface.
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