TY - JOUR
T1 - Interleukin-6 receptor blockade improves bone healing following ischemic osteonecrosis in adolescent mice
AU - Kuroyanagi, Gen
AU - Kamiya, Nobuhiro
AU - Yamaguchi, Ryosuke
AU - Kim, Harry K.W.
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Adolescent ischemic osteonecrosis
KW - Animal model
KW - Cartilage
KW - IL-6 receptor blockade
KW - Legg-Calve-Perthes disease
KW - VEGF
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U2 - 10.1016/j.ocarto.2023.100386
DO - 10.1016/j.ocarto.2023.100386
M3 - Article
C2 - 37600923
AN - SCOPUS:85166934362
SN - 2665-9131
VL - 5
JO - Osteoarthritis and Cartilage Open
JF - Osteoarthritis and Cartilage Open
IS - 4
M1 - 100386
ER -