Reduced TGF-β Expression and CD206-Positive Resident Macrophages in the Intervertebral Discs of Aged Mice

Yokozeki, Yuji; Kawakubo, Ayumu; Miyagi, Masayuki; Kuroda, Akiyoshi; Sekiguchi, Hiroyuki; Inoue, Gen; Takaso, Masashi; Uchida, Kentaro

doi:10.1155/2021/7988320

Cited by 10 publications

(12 citation statements)

References 32 publications

(40 reference statements)

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“…Sample size for PCR analysis was determined based on our previous studies. 6 , 26 Power analysis with an alpha of 0.05 and power of 0.80 was conducted using G*POWER3 to determine a sufficient sample size for each analysis, except PCR analysis. IVDs were resected without separating the NP and AF, and pooled for each experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Sample size ( n = 10) for PCR analysis of Cd206 was determined based on our previous study. 26 The puncture model was created in 30 C57BL/6J mice, with random and equal assignation to the vehicle or treatment groups. One group received intraperitoneal (IP) injection with 10 mg/kg SB431542 in a 5% DMSO solution while the second received IP injection with 5% DMSO solution (vehicle) at PPD 5 and PPD 6.…”

Section: Methodsmentioning

confidence: 99%

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Origin of M2 Mϕ and its macrophage polarization by TGF-β in a mice intervertebral injury model

Kawakubo

Miyagi

Yokozeki

et al. 2022

Int J Immunopathol Pharmacol

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Introduction Studies have identified the presence of M1 and M2 macrophages (Mϕ) in injured intervertebral discs (IVDs). However, the origin and polarization-regulatory factor of M2 Mϕ are not fully understood. TGF-β is a regulatory factor for M2 polarization in several tissues. Here, we investigated the source of M2 Mϕ and the role of TGF-β on M2 polarization using a mice disc-puncture injury model. Methods To investigate the origin of M2 macrophages, 30 GFP chimeric mice were created by bone marrow transplantation. IVDs were obtained from both groups on pre-puncture (control) and post-puncture days 1, 3, 7, and 14 and CD86 (M1 marker)- and CD206 (M2 marker)-positive cells evaluated by flow cytometry ( n = 5 at each time point). To investigate the role of TGF-β on M2 polarization, TGF-β inhibitor (SB431542) was also injected on post-puncture days (PPD) 5 and 6 and CD206 expression was evaluated on day 7 by flow cytometry ( n = 5) and real time PCR ( n = 10). Results The proportion of CD86+ Mϕ within the GFP+ population was significantly increased at PPD 1, 3, 7, and 14 compared to control. CD206-positive cells in GFP-populations were significantly increased on PPD 7 and 14. In addition, the percentage of CD206-positive cells was significantly higher in GFP-populations than in GFP+ populations. TGF-β inhibitor reduced CD206-positive cells and Cd206 expression at 7 days after puncture. Conclusion Our findings suggest that M2 Mϕ following IVD injury may originate from resident Mϕ. TGF-β is a key factor for M2 polarization of macrophages following IVD injury.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Origin of M2 Mϕ and its macrophage polarization by TGF-β in a mice intervertebral injury model

Kawakubo

Miyagi

Yokozeki

et al. 2022

Int J Immunopathol Pharmacol

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“…Similarly, CD206 may also play an important role in the antiinflammatory ability of SMs. Yokozeki et al (67) injected TGFb inhibitor (SB431542) intraperitoneally into C57BL/6J mice and used real-time PCR to detect the expression of CD206 in intervertebral disc macrophages, in which the proportion of CD206 + macrophages was found to be significantly reduced. At the same time, CD206 + macrophages have also been shown to regulate the IL-6-mediated paracrine mechanism in order to combat fibrosis in fibroblasts (68).…”

Section: Anti-inflammatory Surface Markers: Cd163 Cd206 and F4/80mentioning

confidence: 99%

Synovial Macrophages: Past Life, Current Situation, and Application in Inflammatory Arthritis

Bai

Xue-Xue

et al. 2022

Front. Immunol.

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Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients’ quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.

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“…The expression of IL-1β, TNF-α, vascular endothelial growth factor (VEGF) and its receptor basic fibroblast growth factor (BFGF) are up-regulated in degenerative IVD, the catabolism of neovascularization is accelerated, and MMP synthesis is increased ( Risbud and Shapiro, 2014 ). Yokozeki et al (2021) documented that TGF-β can regulate resident macrophages in adult mice in addition to its self-regulatory effect, and age-related decline in TGF-β expression leads to decreased amount of macrophages in IVD, which is critical for tissue homeostasis and immune regulation. Hence, the excessively decrease in macrophages may result in imbalance homeostasis of IVD microenvironment, triggering or exacerbating LBP.…”

Section: Introductionmentioning

confidence: 99%

New Progress in Basic Research of Macrophages in the Pathogenesis and Treatment of Low Back Pain

Yan

Song

Kou

et al. 2022

Front. Cell Dev. Biol.

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Low back pain (LBP) is quite common in clinical practice, which can lead to long-term bed rest or even disability. It is a worldwide health problem remains to be solved. LBP can be induced or exacerbated by abnormal structure and function of spinal tissue such as intervertebral disc (IVD), dorsal root ganglion (DRG) and muscle; IVD degeneration (IVDD) is considered as the most important among all the pathogenic factors. Inflammation, immune response, mechanical load, and hypoxia etc., can induce LBP by affecting the spinal tissue, among which inflammation and immune response are the key link. Inflammation and immune response play a double-edged sword role in LBP. As the main phagocytic cells in the body, macrophages are closely related to body homeostasis and various diseases. Recent studies have shown that macrophages are the only inflammatory cells that can penetrate the closed nucleus pulposus, expressed in various structures of the IVD, and the number is positively correlated with the degree of IVDD. Moreover, macrophages play a phagocytosis role or regulate the metabolism of DRG and muscle tissues through neuro-immune mechanism, while the imbalance of macrophages polarization will lead to more inflammatory factors to chemotaxis and aggregation, forming an “inflammatory waterfall” effect similar to “positive feedback,” which greatly aggravates LBP. Regulation of macrophages migration and polarization, inhibition of inflammation and continuous activation of immune response by molecular biological technology can markedly improve the inflammatory microenvironment, and thus effectively prevent and treat LBP. Studies on macrophages and LBP were mainly focused in the last 3–5 years, attracting more and more scholars’ attention. This paper summarizes the new research progress of macrophages in the pathogenesis and treatment of LBP, aiming to provide an important clinical prevention and treatment strategy for LBP.

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Reduced TGF-β Expression and CD206-Positive Resident Macrophages in the Intervertebral Discs of Aged Mice

Cited by 10 publications

References 32 publications

Origin of M2 Mϕ and its macrophage polarization by TGF-β in a mice intervertebral injury model

Origin of M2 Mϕ and its macrophage polarization by TGF-β in a mice intervertebral injury model

Synovial Macrophages: Past Life, Current Situation, and Application in Inflammatory Arthritis

New Progress in Basic Research of Macrophages in the Pathogenesis and Treatment of Low Back Pain

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