Karamchedu Naga Padmini, Fleming Braden C, Donnenfield Jonah I, Proffen Benedikt L, Costa Meggin Q, Molino Janine, Murray Martha M
Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital Providence, RI, USA.
Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School Boston, MA, USA.
Am J Transl Res. 2021 Jul 15;13(7):7667-7676. eCollection 2021.
The roles that cytokines and matrix metalloproteinases play in the onset and progression of posttraumatic osteoarthritis (PTOA) remain a topic of debate. The study objective was to evaluate the concentrations of these inflammatory mediators during the development of mild to moderate PTOA in the porcine anterior cruciate ligament (ACL) surgical model. We hypothesized that there would be more animals with detectable mediators in the pigs that develop moderate PTOA (those receiving ACL reconstruction or untreated ACL transection) compared to those that develop mild PTOA (those receiving scaffold-enhanced ACL repair). 36 Yucatan minipigs underwent ACL transection and were randomized to: 1) no further treatment, 2) ACL reconstruction, or 3) scaffold-enhanced ACL repair. Synovial fluid samples were obtained pre-operatively, and at 1, 4, 12, 26 and 52 weeks post-operatively. The concentrations of inflammatory mediator in the synovial fluid samples were evaluated via multiplex assay. Macroscopic cartilage assessments were performed following euthanasia at 52 weeks. As found in prior studies, the repair group had significantly less cartilage damage than either the ACL transected or ACL reconstruction groups (P<.03). The presence and concentrations of the biomarkers were influenced by surgical group and time. In general, the concentrations of inflammatory mediators were higher in the repair group, which exhibited less cartilage damage than the other two treatment groups. While this finding disproved the hypotheses, these data suggest that the metabolic activity of the joints exhibiting less cartilage damage remained higher over the 52-week period than those that did not.
细胞因子和基质金属蛋白酶在创伤后骨关节炎(PTOA)发病和进展过程中所起的作用仍是一个争论的话题。本研究的目的是在猪前交叉韧带(ACL)手术模型中,评估这些炎症介质在轻至中度PTOA发展过程中的浓度。我们假设,与发生轻度PTOA的猪(接受支架增强ACL修复的猪)相比,发生中度PTOA的猪(接受ACL重建或未治疗的ACL横断的猪)中,会有更多动物可检测到这些介质。36只尤卡坦小型猪接受了ACL横断,并被随机分为:1)不进一步治疗,2)ACL重建,或3)支架增强ACL修复。在术前、术后1周、4周、12周、26周和52周采集滑液样本。通过多重分析评估滑液样本中炎症介质的浓度。在52周时实施安乐死后进行宏观软骨评估。如先前研究中所发现的,修复组的软骨损伤明显少于ACL横断组或ACL重建组(P<0.03)。生物标志物的存在和浓度受手术组和时间的影响。一般来说,修复组中炎症介质的浓度较高,其软骨损伤比其他两个治疗组少。虽然这一发现推翻了假设,但这些数据表明,在52周期间,软骨损伤较少的关节的代谢活性仍高于损伤较多的关节。