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Published on: September 16, 2020
Interleukin-6 receptor blockade improves bone healing following ischemic osteonecrosis in adolescent mice
Gen Kuroyanagi1,2, Nobuhiro Kamiya1,3, Ryosuke Yamaguchi1,4
1Center for Excellence in Hip, Scottish Rite for Children, Dallas, TX 75219, USA.
Insights
Blocking interleukin-6 (IL-6) receptor in adolescent mice with juvenile ischemic osteonecrosis (JIO) significantly improved bone healing. This targeted therapy enhanced bone formation and revascularization, offering a potential treatment for this challenging hip disorder.
Area of Science:
- Orthopedics
- Immunology
- Regenerative Medicine
Background:
- Juvenile ischemic osteonecrosis (JIO) of the femoral head is a severe childhood hip disorder leading to permanent deformity.
- Interleukin-6 (IL-6) is elevated in JIO hip synovial fluid, with articular chondrocytes being a primary source.
- Adolescent JIO presents significant treatment challenges and poor outcomes.
Purpose of the Study:
- To investigate if blocking the IL-6 receptor can prevent bone loss in adolescent JIO.
- To determine if IL-6 receptor blockade improves bone healing in adolescent JIO.
- To evaluate the therapeutic potential of IL-6 receptor blockers for adolescent JIO.
Main Methods:
- Adolescent mice (12-week-old) underwent surgical induction of JIO.
- Mice were treated with either saline (control) or MR16-1, an IL-6 receptor blocker.
- Bone microarchitecture, histomorphometry, and revascularization were assessed.
Main Results:
- MR16-1 treatment significantly increased bone volume and trabecular bone thickness.
- Histomorphometry revealed increased osteoblast numbers, bone formation rate, and mineral apposition rate.
- Significant improvements in revascularization and restoration of necrotic marrow were observed, with increased VEGF expression.
Conclusions:
- IL-6 receptor blockade effectively enhanced bone formation and revascularization in adolescent mice with JIO.
- These findings support IL-6 receptor blockers as a promising medical therapy for adolescent JIO.
- Targeting IL-6 signaling may offer a novel therapeutic strategy for improving outcomes in JIO.
Objective:
Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL-6) is significantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL-6. Adolescent JIO is particularly challenging to treat and has poor outcome. This study determined if IL-6 receptor blockade prevents bone loss and improves the bone healing in adolescent JIO.
Method:
Adolescent mice (12-week-old) surgically induced with JIO were treated with either saline or MR16-1, an IL-6 receptor blocker.
Results:
Micro-CT assessment showed significantly increased bone volume (p < 0.001, Cohen's d = 2.0) and trabecular bone thickness (p < 0.001, d = 2.3) after the MR16-1 treatment. Histomorphometric assessment showed significantly increased osteoblast number (p < 0.01, d = 2.3), bone formation rate (p < 0.01, d = 4.3), and mineral apposition rate (p < 0.01, d = 4.1) after the MR16-1 treatment. The number of osteoclasts was unchanged. Histologic assessment showed significantly increased revascularization (p < 0.01) and restoration of the necrotic marrow with new hematopoietic bone marrow (p < 0.01). Vascular endothelial growth factor (VEGF) expression was increased in the revascularized area and the articular cartilage, and in the cultured chondrocytes treated with IL-6 receptor inhibitor.
Conclusion:
IL-6 blockade in adolescent mice with JIO enhanced bone formation and revascularization. The findings suggest IL-6 receptor blocker as a potential medical therapy for adolescent JIO.
