NOD2 negatively regulated titanium particle-induced osteolysis in mice

Li, Shixun; Qiu, Junxiong; Qin, Ling; Peng, Peng; Li, Changchuan; Mao, Jiaji; Fang, Guibin; Chen, Zhong; Lin, Sipeng; Fu, Yuan; Cai, Weibin; Ding, Yue

doi:10.1039/c9bm00306a

Cited by 13 publications

(11 citation statements)

References 30 publications

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“…M1 phenotype macrophages play a defensive role when interacting with biological materials. They perform phagocytic functions to remove pathogens and debris from injury sites and perform proinflammatory functions by secreting TNF- α , IL-1, and IL-6 [ 23 ]. M2 phenotype macrophages exert anti-inflammatory effects and secrete interleukin-10 (IL-10) [ 24 ].…”

Section: Exosomes and Macrophage Polarizationmentioning

confidence: 99%

Exosome: Function and Application in Inflammatory Bone Diseases

Wang

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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In the skeletal system, inflammation is closely associated with many skeletal disorders, including periprosthetic osteolysis (bone loss around orthopedic implants), osteoporosis, and rheumatoid arthritis. These diseases, referred to as inflammatory bone diseases, are caused by various oxidative stress factors in the body, resulting in long-term chronic inflammatory processes and eventually causing disturbances in bone metabolism, increased osteoclast activity, and decreased osteoblast activity, thereby leading to osteolysis. Inflammatory bone diseases caused by nonbacterial factors include inflammation- and bone resorption-related processes. A growing number of studies show that exosomes play an essential role in developing and progressing inflammatory bone diseases. Mechanistically, exosomes are involved in the onset and progression of inflammatory bone disease and promote inflammatory osteolysis, but specific types of exosomes are also involved in inhibiting this process. Exosomal regulation of the NF-κB signaling pathway affects macrophage polarization and regulates inflammatory responses. The inflammatory response further causes alterations in cytokine and exosome secretion. These signals regulate osteoclast differentiation through the receptor activator of the nuclear factor-kappaB ligand pathway and affect osteoblast activity through the Wnt pathway and the transcription factor Runx2, thereby influencing bone metabolism. Overall, enhanced bone resorption dominates the overall mechanism, and over time, this imbalance leads to chronic osteolysis. Understanding the role of exosomes may provide new perspectives on their influence on bone metabolism in inflammatory bone diseases. At the same time, exosomes have a promising future in diagnosing and treating inflammatory bone disease due to their unique properties.

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Section: Exosomes and Macrophage Polarizationmentioning

confidence: 99%

Exosome: Function and Application in Inflammatory Bone Diseases

Wang

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…In addition, the ZBTB20 knockout was reported to decrease the serum levels of IL-6 and TNF-α in LPS-treated mice [20]. AS is an inflammatory disease, and NF-κB functions as a major transcription factor in inflamma-tory and immune responses [43,44]. Thus, we further examined the roles of the ZBTB20 knockdown on NF-κB activities, and we found that the ox-LDL stimulation increased the activities of macrophage NF-κB signaling, which was consistent with findings from previous studies [45,46].…”

mentioning

confidence: 99%

ZBTB20 Positively Regulates Oxidative Stress, Mitochondrial Fission, and Inflammatory Responses of ox-LDL-Induced Macrophages in Atherosclerosis

Tao

Qiu

et al. 2021

Oxidative Medicine and Cellular Longevity

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Atherosclerosis (AS) is one of the most serious and common cardiovascular diseases affecting human health. AS is featured by the accumulation of plaques in vessel walls. The pathophysiology of AS is relevant in the low-density lipoprotein (LDL) uptake by macrophages, as well as the conversion of macrophages to foam cells. However, the mechanisms about how macrophages regulate AS have not been fully elucidated. In this study, we aimed to illuminate the roles of ZBTB20 and to excavate the underlying regulative mechanisms of ZBTB20 in AS. The microarray analysis revealed that ZBTB20 was a hub gene in the oxidative stress and inflammatory responses induced by oxidized LDL (ox-LDL) in AS. Correspondingly, our validation studies showed that ZBTB20 increased in either the human atherosclerotic lesion or the ox-LDL-stimulated macrophages. Moreover, the knockdown of ZBTB20 decreased M1 polarization, suppressed the proinflammatory factors, inhibited mitochondrial fission, and reduced the oxidative stress level of macrophages induced by ox-LDL. The mechanistic studies revealed that the ZBTB20 knockdown suppressed NF-κB/MAPK activation and attenuated the mitochondrial fission possibly via regulating the nucleus translocation of NRF2, a pivotal transcription factor on redox homeostasis. Our in vivo studies showed that the sh-ZBTB20 adenovirus injection could reduce the progression of AS in apolipoprotein E-deficient (ApoE-/-) mice. All in all, these results suggested that ZBTB20 positively regulated the oxidative stress level, mitochondrial fission, and inflammatory responses of macrophages induced by ox-LDL, and the knockdown of ZBTB20 could attenuate the development of AS in ApoE-/- mice.

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“…After revealing the role of p110δ and KLF4 in TiPs caused macrophages inflammation, we generated nude mice cranial osteolysis model according to the previous researches for vivo experiments [ 31 , 36 ], and grouping was described in Methods section. At day 7 after surgery, we could detect strong luciferase signal, which meant that macrophages remained on the calvaria.…”

Section: Resultsmentioning

confidence: 99%

MiR-92a/KLF4/p110δ regulates titanium particles-induced macrophages inflammation and osteolysis

Wen

Lin

et al. 2022

Cell Death Discov.

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As total joint replacement is widely applied for severe arthropathy, peri-prosthetic aseptic loosening as one of the main causes of implant failure has drawn wide attention. Wear particles such as titanium particles (TiPs) derived from prosthesis can initiate macrophages inflammation and sequentially activate osteoclasts, which results in bone resorption and osteolysis for long-term. Therefore, inhibiting wear particles induced macrophages inflammation is considered as a promising therapy for AL. In this research, we found that the inhibition of p110δ, a member of class IA PI3Ks family, could significantly dampen the TiPs-induced secretion of TNFα and IL-6. By the transfection of siRNA targeting p110δ, we confirmed that p110δ was responsible for TNFα and IL-6 trafficking out of Golgi complex without affecting their expression in TiPs-treated macrophages. As the upstream transcription-repressor of p110δ, Krüppel-like factor 4 (KLF4), targeted by miR-92a, could also attenuate TiPs-induced inflammation by mediating NF-κB pathway and M1/M2 polarization. To further ascertain the roles of KLF4/p110δ, TiPs-induced mice cranial osteolysis model was established and vivo experiments validated that KLF4-knockdown could exacerbate TiPs-induced osteolysis, which was strikingly ameliorated by knockdown of p110δ. In summary, our study suggests the key role of miR-92a/KLF4/p110δ signal in TiPs-induced macrophages inflammation and osteolysis.

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NOD2 negatively regulated titanium particle-induced osteolysis in mice

Abstract: NOD2 protects mice from titanium particle-induced osteolysis.

Cited by 13 publications

References 30 publications

Exosome: Function and Application in Inflammatory Bone Diseases

Exosome: Function and Application in Inflammatory Bone Diseases

ZBTB20 Positively Regulates Oxidative Stress, Mitochondrial Fission, and Inflammatory Responses of ox-LDL-Induced Macrophages in Atherosclerosis

MiR-92a/KLF4/p110δ regulates titanium particles-induced macrophages inflammation and osteolysis

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