Peng-Fei Han1, Lei Wei2, Zhi-Qing Duan3, Zhi-Liang Zhang1, Tao-Yu Chen1, Jian-Gong Lu1, Rui-Peng Zhao1, Xiao-Ming Cao1, Peng-Cui Li1, Zhi Lv1, Xiao-Chun Wei4. 1. Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, PR China. 2. Department of Orthopaedics, The Alpert Medical School of Brown University, Providence, RI, USA. 3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, PR China. 4. Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi, PR China. Electronic address: sdeygksys@163.com.
Abstract
BACKGROUND: It has been noted that anterior cruciate ligament (ACL) injury-induced cartilage degeneration is the key risk factor for post-traumatic osteoarthritis (PTOA). However, whether the cartilage degeneration after ACL injury is caused by inflammation, abnormal biomechanics or both remains largely unknown, as there has been no animal model for separating the two factors so far. METHODS: Eighteen-month-old female mini-pigs were divided into an "idealized" anterior cruciate ligament reconstruction (IACLR) group and a control group (n = 16 limbs per group). Real-time PCR, safranine O staining and indian ink staining were performed to verify whether animal models were successfully established or not. Multiple linear regression analysis was used to evaluate the correlation between levels of the inflammatory factors (including interferon [IFN]-γ, interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor [TNF]-α measured by the Luminex method) and changes in cartilage histology (quantified by morphological scoring) after surgery. RESULTS: A significant OA cartilage damage with increased MMP-1, MMP-13 mRNA levels and reduced aggrecan mRNA/protein levels was observed in IACLR groups. As a result, the IACLR gross morphology score was dramatically increased than control. Moreover, IACLR significantly increased the levels of IL-1β, IL-4, IL-6 and TNF-α in the synovial fluid of the knee. Most importantly, a close relationship was found between IL-1β, IL-6 and TNF-α concentrations and morphological score of PTOA, respectively. CONCLUSION: These results demonstrated that inflammatory factors are independently responsible for the onset of PTOA.
BACKGROUND: It has been noted that anterior cruciate ligament (ACL) injury-induced cartilage degeneration is the key risk factor for post-traumatic osteoarthritis (PTOA). However, whether the cartilage degeneration after ACL injury is caused by inflammation, abnormal biomechanics or both remains largely unknown, as there has been no animal model for separating the two factors so far. METHODS: Eighteen-month-old female mini-pigs were divided into an "idealized" anterior cruciate ligament reconstruction (IACLR) group and a control group (n = 16 limbs per group). Real-time PCR, safranine O staining and indian ink staining were performed to verify whether animal models were successfully established or not. Multiple linear regression analysis was used to evaluate the correlation between levels of the inflammatory factors (including interferon [IFN]-γ, interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor [TNF]-α measured by the Luminex method) and changes in cartilage histology (quantified by morphological scoring) after surgery. RESULTS: A significant OA cartilage damage with increased MMP-1, MMP-13 mRNA levels and reduced aggrecan mRNA/protein levels was observed in IACLR groups. As a result, the IACLR gross morphology score was dramatically increased than control. Moreover, IACLR significantly increased the levels of IL-1β, IL-4, IL-6 and TNF-α in the synovial fluid of the knee. Most importantly, a close relationship was found between IL-1β, IL-6 and TNF-α concentrations and morphological score of PTOA, respectively. CONCLUSION: These results demonstrated that inflammatory factors are independently responsible for the onset of PTOA.
Authors: Tyler Barker; Victoria E Rogers; Vanessa T Henriksen; Roy H Trawick; Nathan G Momberger; G Lynn Rasmussen Journal: Sci Rep Date: 2021-01-19 Impact factor: 4.379
Authors: Ryan P Donahue; Jarrett M Link; Vijaykumar S Meli; Jerry C Hu; Wendy F Liu; Kyriacos A Athanasiou Journal: Cartilage Date: 2022 Jan-Mar Impact factor: 3.117