Histological Evidence of Increased Osteoclast Cell Number and Asymmetric Bone Resorption Activity in the Tibiae of Interleukin-6-Deficient Mice.
Interleukin-6 (IL-6) is a multifunctional cytokine considered to modulate bone homeostasis. Based on previous contradictory studies, we aimed to verify the influence of IL-6 deficiency on bone remodeling using an IL-6 knockout (IL-6-/-) murine model. Eight-month-old male mice, homozygous for the disrupted IL-6 gene, and their wild type (WT) littermates (control), were used. After transcardiac perfusion, tibiae were removed for histochemical analysis. Compared with the control group, IL-6 deficiency increased tartrate resistant acid phosphatase (TRAP)-positive osteoclast numbers and up-regulated the alkaline phosphatase (ALP) activity of osteoblasts in the metaphysis of the tibia. However, further analysis of serial histological sections from IL-6-/- mice found a significant discrepancy in osteoclast number, with the higher number of TRAP-positive osteoclasts conflicting with the lower number of cathepsin K-positive osteoclasts. Moreover, TUNEL staining identified a significantly higher rate of osteoclast apoptosis in IL-6-/- mice as compared with their WT controls. IL-6 deficiency induced abundant TRAP-positive osteoclasts but delayed bone remodeling by significantly inhibiting the bone resorption activity of osteoclasts and promoting osteoclast apoptosis.
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Hongrui
H
Liu
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Wei
W
Feng
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Yimin
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Jian
J
Cui
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Shengyu
S
Lv
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Tomoka
T
Hasegawa
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Bao
B
Sun
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Juan
J
Li
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Kimimitsu
K
Oda
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Norio
N
Amizuka
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO) liminqi@sdu.edu.cn.
Minqi
M
Li
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D016723:Bone Remodeling; D001862:Bone Resorption / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology*; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D013977:Tibia / Q000473:pathology*
D015850:Interleukin-6; D000469:Alkaline Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
IL-6; apoptosis; bone resorption; osteoblast; osteoclast