title: Inhibition of titanium-particle-induced inflammatory osteolysis after local administration of dopamine and suppression of osteoclastogenesis via D2-like receptor signaling pathway.
abstract: Chronic inflammation and extensive osteoclast formation play critical roles in wear-debris-induced peri-implant osteolysis. We investigated the potential impact of dopamine on titanium-particle-induced inflammatory osteolysis in vivo and in vitro. Twenty-eight C57BL/6J mice were randomly assigned to four groups: sham control (PBS treatment), titanium (titanium/PBS treatment), low- (titanium/2 μg kg(-1) day(-1) dopamine) and high-dopamine (titanium/10 μg kg(-1) day(-1) dopamine). After 2 weeks, mouse calvariae were collected for micro-computed tomography (micro-CT) and histomorphometry analysis. Bone-marrow-derived macrophages (BMMs) were isolated to assess osteoclast differentiation. Dopamine significantly reduced titanium-particle-induced osteolysis compared with the titanium group as confirmed by micro-CT and histomorphometric data. Osteoclast numbers were 34.9% and 59.7% (both p < 0.01) lower in the low- and high-dopamine-treatment groups, respectively, than in the titanium group. Additionally, low RANKL, tumor necrosis factor-α, interleukin-1β and interleukin-6 immunochemistry staining were noted in dopamine-treatment groups. Dopamine markedly inhibited osteoclast formation, osteoclastogenesis-related gene expression and pro-inflammatory cytokine expression in BMMs in a dose-dependent manner. Moreover, the resorption area was decreased with 10(-9) M and 10(-8) M dopamine to 40.0% and 14.5% (both p < 0.01), respectively. Furthermore, the inhibitory effect of dopamine was reversed by the D2-like-receptor antagonist haloperidol but not by the D1-like-receptor antagonist SCH23390. These results suggest that dopamine therapy could be developed into an effective and safe method for osteolysis-related disease caused by chronic inflammation and excessive osteoclast formation.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China.
authors.forename: Yaozeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Soochow University, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China; Department of Orthopedics, Soochow University Affiliated First People's Hospital of Changshou City, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Orthopedic Institute, Soochow University, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China.
authors.forename: Hongguo
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China.
authors.forename: Zichuan
authors.initials: Z
authors.lastname: Ping
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China.
authors.forename: Xuanyang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, China. Electronic address: szgengdc@163.com.
authors.forename: Dechun
authors.initials: D
authors.lastname: Geng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010014:Osteolysis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D053245:RANK Ligand / Q000032:analysis; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000187:drug effects / Q000473:pathology; D014025:Titanium / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055114:X-Ray Microtomography
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D053245:RANK Ligand; D017448:Receptors, Dopamine D2; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium; D004298:Dopamine
keywords: Aseptic loosening; Dopamine; Inflammation; Osteoclast; Wear debris