Icariin protects against titanium particle-induced osteolysis and inflammatory response in a mouse calvarial model

Liang

J of Cellular Biochemistry

et al. 2018

Wear particle–induced bone resorption leads to prosthesis loosening, which is a major complication associated with total joint arthroplasty. Although the exact mechanism remains unclear, wear particle–induced extensive osteoclastogenesis plays a critical role in this process. Thus, a potential treatment of prosthetic loosening is focused on suppressing extensive osteoclast formation and bone resorption, which prevents wear particle–induced osteolysis. Arctigenin isolated from Arctium lappa has numerous beneficial pharmacologic effects, including anti‐inflammatory, antiviral, and anticancer activities. Here, we explored the potential impact of arctigenin on titanium (Ti) particle–induced osteolysis in vivo. Our data showed that arctigenin significantly suppressed Ti particle–induced osteolysis and prevented bone destruction compared with Ti group. In addition, the number of osteoclasts reduced after treatment with arctigenin in vivo, indicating osteoclastogenesis might be inhibited by arctigenin. Next, bone marrow–derived macrophages were used to examine osteoclast differentiation, bone resorption, and activation of osteoclast‐related signaling pathways. The results showed that arctigenin inhibited RANKL‐induced osteoclastogenesis without any cytotoxicity and suppressed osteoclastic marker genes expression and hydroxyapatite resorption activity in a dose‐dependent manner. Additionally, arctigenin suppressed receptor activator of nuclear factor κΒ (NF‐κB) ligand–induced NF‐κB activation, concomitant with retarded IκBɑ degradation and inhibition of p65 nuclear translocation, leading to impaired osteoclastogenesis. Collectively, our results suggest that arctigenin is a promising candidate for the treatment of osteoclast‐related osteolytic diseases caused by excessive osteoclast formation.

Section: Discussionsupporting

confidence: 61%

Arctigenin inhibits RANKL‐induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle–induced bone loss in vivo

Liang

J of Cellular Biochemistry

et al. 2018

“…Li et al applied ICA at a dosage of 40 mg/kg in a murine osteoporotic model and found no adverse effect in the body and uterine weight of ovariectomized mice [61]. The safety of ICA was also confirmed by other in vivo studies [47,58,62]. Moreover, ICA has been used safely for up to eight weeks in one clinical trial [63].…”

Section: Discussionmentioning

confidence: 97%

“…All animals underwent the complete detachment and immediate repair of the right supraspinatus tendon with bone tunnel suture fixation, as described previously [67,68,69,70,71]. Once the rat RCT model was established, animals in the ICA group were gavage-fed daily with ICA at 0.125 mg/g [20,21,62], while animals in the control group received the same volume of saline. The animals were then sacrificed in a CO 2 chamber at two or four weeks postoperatively ( n = 16 in each group at each time point).…”

Section: Methodsmentioning

confidence: 99%

Icariin Promotes Tendon-Bone Healing during Repair of Rotator Cuff Tears: A Biomechanical and Histological Study

Zhang

Wang

et al. 2016

IJMS

To investigate whether the systematic administration of icariin (ICA) promotes tendon-bone healing after rotator cuff reconstruction in vivo, a total of 64 male Sprague Dawley rats were used in a rotator cuff injury model and underwent rotator cuff reconstruction (bone tunnel suture fixation). Rats from the ICA group (n = 32) were gavage-fed daily with ICA at 0.125 mg/g, while rats in the control group (n = 32) received saline only. Micro-computed tomography, biomechanical tests, serum ELISA (calcium; Ca, alkaline phosphatase; AP, osteocalcin; OCN) and histological examinations (Safranin O and Fast Green staining, type I, II and III collagen (Col1, Col2, and Col3), CD31, and vascular endothelial growth factor (VEGF)) were analyzed two and four weeks after surgery. In the ICA group, the serum levels of AP and OCN were higher than in the control group. More Col1-, Col2-, CD31-, and VEGF-positive cells, together with a greater degree of osteogenesis, were detected in the ICA group compared with the control group. During mechanical testing, the ICA group showed a significantly higher ultimate failure load than the control group at both two and four weeks. Our results indicate that the systematic administration of ICA could promote angiogenesis and tendon-bone healing after rotator cuff reconstruction, with superior mechanical strength compared with the controls. Treatment for rotator cuff injury using systematically-administered ICA could be a promising strategy.

J of Periodontal Research

“…Commercially pure titanium particles (catalog #00681, Ward Hill, Massachusetts, USA, 90% size < 3.6 μm, mean size = 3.32 ± 2.39 μm) were treated with nitric acid to remove endotoxins as previously described …”

Section: Methodsmentioning

confidence: 99%

Macrophage polarization in aseptic bone resorption around dental implants induced by Ti particles in a murine model

Wang

Liu

Feng

et al. 2019

Background and Objectives Titanium particles/ions detected in peri‐implant tissues have been considered as a potential etiologic factor for crestal bone loss around oral implants. However, the definite impact of titanium wear particles on the health of surrounding structures remains undetermined. The purpose of this study was to investigate the effects of titanium particles‐induced foreign body reaction on peri‐implant bone level and the related mechanism by using clodronate liposomes to deplete macrophages. Material and Methods Sprague Dawley rats with custom‐made titanium screw implanted in bilateral maxillary first molar area for 4 weeks to obtain osseointegration were randomly divided into four groups. Twenty microgram titanium particles were introduced into the peri‐implant tissue to induce aseptic foreign body reaction, and macrophages were depleted by the local injection of 100 μL clodronate liposome immediately and re‐injection every 3 days until the sacrifice of the rats (Ti + LipClod group). Titanium‐injected rats also treated with phosphate buffer solution (Ti + PBS) or empty liposome (Ti + Lip) as well as rats injected with PBS alone (Control) were included as controls. Eight weeks later, animals were sacrificed and samples containing implants were collected. Half of the samples were analyzed radiologically to measure bone level change, and macrophage markers (CD68, CCR7, CD163) was also characterized by immunofluorescence to evaluate macrophage number, density, and phenotype distribution (CCR7+M1/CD163+M2). The rest of the samples were used to determine the relative mRNA expression levels of TNF‐α, IL‐1β, IL‐6, and RANKL with real‐time PCR analysis. Results No obvious bacterial contamination was found in all titanium‐injected areas, and the implant survival rate was 100% with no implant loss. Compared with Ti + PBS and Ti + Lip group, macrophage density (1.64 ± 0.86%) infiltrated into peri‐implant tissue and bone loss (0.17 ± 0.03 mm) around implant decreased significantly in the Ti + LipClod group. Immunofluorescence analysis showed that more macrophage infiltrated into peri‐implant tissue in the Ti + PBS and Ti + Lip groups, predominantly with M1 phenotype. In contrast, the macrophage density was lower and M2 phenotype was dominant in the Control group, while macrophages density was significantly reduced and the M1 type macrophages were slightly more than M2 type in the Ti + LipClod group. Accordingly, TNF‐α, IL‐1β, IL6, and RANKL mRNA expression increased significantly in the Ti + PBS and Ti + Lip groups compared with Control and Ti + LipClod groups. Conclusions Titanium particles had a negative effect on peri‐implant tissue by activating macrophages which induced an M1 macrophage phenotype promoting local secretion of inflammatory cytokines. It was found that clodronate liposome treatment attenuated the severity of inflammation and bone loss by depletion of macrophages. Therefore, the present study revealed the marked impact of macrophage polarization with respect to peri‐implant bone loss caused...