Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection.

Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection.
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DOI:
10.1002/art.27550
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发表时间:
2010-08
影响因子:
--
通讯作者:
Elsaid, Khaled A.
Elsaid, Khaled A.
中科院分区:
其他
文献类型:
--
作者:
Jay, Gregory D.;Fleming, Braden C.;Watkins, Bryn A.;McHugh, Karen A.;Anderson, Scott C.;Zhang, Ling X.;Teeple, Erin;Waller, Kimberly A.;Elsaid, Khaled A.

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研究在前交叉韧带(ACL)损伤大鼠模型中,关节内注射来源于培养的人滑膜细胞(HSL)、重组蛋白(rhPRG 4)或人滑液(HSFL)的润滑素后,软骨退化是否得到预防或最小化。在刘易斯大鼠(n=45)中进行单侧ACL横断(ACLT)。在损伤后第7天开始关节内注射(50μl/注射)PBS(n =9)、HSL(n=9; 200μg/ml)、rhPRG 4(n=9; 200μg/ml)和HSFL(n=9; 200μg/ml),每周持续两次。在损伤后第32天收获动物。采用番红O/Fast绿色染色进行组织学分析,盲法研究者采用OARSI改良Mankin标准对关节软骨退变进行分级。组织学标本进行润滑素和硫酸化糖胺聚糖免疫探针。在损伤后第17天和第29天进行24小时尿收集,并测量尿CTXII(uCTXII)水平。与无处理或PBS处理相比,用HSL处理导致软骨变性的OARSI评分显著(p<0.05)降低。在润滑素治疗的关节中观察到浅表区软骨细胞和软骨表面上润滑素的免疫染色增加,但未治疗或PBS治疗的关节中没有观察到。在第17天,HSL和HSFL处理的动物的uCTXII水平分别显著低于未处理(p=0.005; p=0.002)和PBS处理(p=0.002; p<0.001)的动物。在本研究中评估的所有类型的润滑素中,ACLT后软骨损伤的减少是明显的,同时II型胶原降解减少。ACL损伤后关节内注射润滑素可能有助于延缓软骨退变和创伤后OA的发展。
To investigate whether cartilage degeneration is prevented or minimized in an anterior cruciate ligament (ACL) injury rat model following intra-articular injections of lubricin derived from human synoviocytes in culture (HSL), recombinant protein (rhPRG4), or from human synovial fluids (HSFL). Unilateral ACL transection (ACLT) was performed in Lewis rats (n=45). Intra-articular injections (50μl/injection) of PBS (n=9), HSL (n=9; 200μg/ml), rhPRG4 (n=9; 200μg/ml) and HSFL (n=9; 200μg/ml) started on day 7 post-injury and continued twice weekly. Animals were harvested on day 32 post-injury. Histological analysis was performed using Safranin O/Fast green stain and blinded investigators graded articular cartilage degeneration using OARSI modified Mankin criteria. Histological specimens were immunoprobed for lubricin and sulphated glycosaminoglycans. 24 hour urine collection was performed on days 17 and 29 post-injury and urinary CTXII (uCTXII) levels were measured. Treatment with HSL resulted in significantly (p<0.05) lower OARSI scores for cartilage degeneration compared to no treatment or PBS treatment. Increased immunostaining for lubricin in the superficial zone chondrocytes and on the surface of cartilage was observed in lubricins-treated but not untreated or PBS-treated joints. On day 17, uCTXII levels of HSL and HSFL-treated animals were significantly lower than untreated (p=0.005; p=0.002) and PBS-treated (p=0.002; p<0.001) animals, respectively. Across all types of lubricin evaluated in this study, a reduction in cartilage damage following ACLT was evident, combined with a reduction in collagen type II degradation. Intraarticular lubricin injection following an ACL injury may be beneficial in retarding cartilage degeneration and development of post-traumatic OA.
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