کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8624767 | 1568104 | 2018 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Interleukin-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis in a murine model
ترجمه فارسی عنوان
حذف اینترلوکین -6 باعث تحریک مجدد رگ های حنجره و ایجاد استخوان جدید در اثر استئوئکوزیسم ایسکمی در یک مدل موش می شود
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
چکیده انگلیسی
Legg-Calvé-Perthes disease (LCPD) is a childhood form of ischemic osteonecrosis of the femoral head which can produce a permanent femoral head deformity and early osteoarthritis. The femoral head deformity results from increased bone resorption and decreased bone formation during repair and remodeling of the necrotic femoral head. A recent study showed that a pro-inflammatory cytokine, interleukin-6 (IL-6), is significantly elevated in the synovial fluid of patients with LCPD. We hypothesized that IL-6 elevation decreases bone formation during the repair process following ischemic osteonecrosis and that IL-6 depletion will increase new bone formation. To test this hypothesis, we surgically induced ischemic osteonecrosis in the wild-type (nâ¯=â¯29) and IL-6 knockout (KO) mice (nâ¯=â¯25). The animals were assessed at 48â¯h, 2â¯weeks and 4â¯weeks following the induction of ischemic osteonecrosis using histologic, histomorphometric and micro-CT methods. IL-6 immunohistochemistry showed high expression of IL-6 in the osteonecrotic side of the wild-type mice at 48â¯h and 4â¯weeks following ischemic osteonecrosis, but not in the IL-6 KO mice. We also confirmed an undetectable level of IL-6 expression in the primary osteoblasts of the IL-6 KO mice compared to the readily detectable level in the wild-type mice. Furthermore, we confirmed that IL-6 deletion did not affect the extent of bone necrosis in the IL-6 KO mice compared to the wild-type mice by performing histologic and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assessments at 2â¯weeks following the induction of ischemia. Both groups had the same extent of ischemic osteonecrosis and absence of repair at 2â¯weeks. At 4â¯weeks, the necrotic epiphyses showed a significant increase in the extent of revascularization in the IL-6 KO mice compared to the wild-type mice (pâ¯=â¯0.001). In addition, a significantly greater recovery of the hematopoietic bone marrow was observed in the osteonecrotic side of the IL-6 KO mice compared to the wild-type mice (pâ¯<â¯0.01). Vascular endothelial growth factor (VEGF) immunohistochemistry showed regionally increased staining in the areas of repair in the osteonecrosis side of IL-6 KO mice compared to the wild-type mice at 4â¯weeks following ischemic osteonecrosis. Micro-CT assessment of the wild-type mice at 4â¯weeks showed a significant decrease in the percent bone volume (pâ¯<â¯0.01) in the osteonecrotic side compared to the control side. In contrast, IL-6 KO mice showed significantly increased bone volume in the osteonecrotic side compared to the osteonecrotic side of WT mice (pâ¯<â¯0.001). No significant difference in the bone volume percentage was found between the control side of the wild-type and the IL-6 KO mice. Histomorphometric analysis at 4â¯weeks revealed increased osteoblast number/bone surface (pâ¯<â¯0.001), bone formation rate (BFR) (pâ¯=â¯0.0001), and mineral apposition rate (MAR) (pâ¯<â¯0.0001) in the osteonecrotic side of the IL-6 KO mice compared to the wild-type mice. The number of osteoclast/bone surface was also increased in the IL-6 KO mice compared to the wild-type mice (pâ¯<â¯0.0001). No significant difference was observed between the control side of the wild-type and IL-6 KO mice with regards to the number of osteoblast or osteoclast/bone surface, BFR, and MAR. We next obtained primary osteoblasts from IL-6 KO mice and showed they expressed a significantly higher level of RANKL/OPG than wild-type mice (pâ¯=â¯0.001) in hypoxia culture condition. Taken together, the findings indicate that IL-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis. This study provides new evidence that therapeutic strategies to block IL-6 may be beneficial for bone healing following ischemic osteonecrosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 116, November 2018, Pages 221-231
Journal: Bone - Volume 116, November 2018, Pages 221-231
نویسندگان
Gen Kuroyanagi, Naga Suresh Adapala, Ryosuke Yamaguchi, Nobuhiro Kamiya, Zhuo Deng, Olumide Aruwajoye, Michael Kutschke, Elena Chen, Chanhee Jo, Yinshi Ren, Harry K.W. Kim,