Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization

Xie, Jing; Wang, Y.; Xiao, Kan; Xu, Hongtao; Luo, Zeyu; Li, L.; Pei, Fuxing; Kraus, Virginia B.; Huang, ZeYu

doi:10.1016/j.joca.2021.04.006

Cited by 25 publications

(17 citation statements)

References 50 publications

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“…Hyaluronic therapy was found to recruit more anti-fibrotic macrophages which also helps in decreasing the pain ( 209 ). In a similar manner, a recent study found that administering alpha defensin-1 makes macrophages anti-inflammatory to an extend and reduces OA in a surgical model ( 210 ). These findings show that targeted anti-inflammatory therapy soon following knee injury may represent a viable future therapeutic strategy, justifying further experimental and, eventually, clinical research in OA.…”

Section: Anti-inflammatory Therapeutics For Oamentioning

confidence: 84%

Obesity, Inflammation, and Immune System in Osteoarthritis

et al. 2022

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Obesity remains the most important risk factor for the incidence and progression of osteoarthritis (OA). The leading cause of OA was believed to be overloading the joints due to excess weight which in turn leads to the destruction of articular cartilage. However, recent studies have proved otherwise, various other factors like adipose deposition, insulin resistance, and especially the improper coordination of innate and adaptive immune responses may lead to the initiation and progression of obesity-associated OA. It is becoming increasingly evident that multiple inflammatory cells are recruited into the synovial joint that serves an important role in pathological changes in the synovial joint. Polarization of macrophages and macrophage-produced mediators are extensively studied and linked to the inflammatory and destructive responses in the OA synovium and cartilage. However, the role of other major innate immune cells such as neutrophils, eosinophils, and dendritic cells in the pathogenesis of OA has not been fully evaluated. Although cells of the adaptive immune system contribute to the pathogenesis of obesity-induced OA is still under exploration, a quantity of literature indicates OA synovium has an enriched population of T cells and B cells compared with healthy control. The interplay between a variety of immune cells and other cells that reside in the articular joints may constitute a vicious cycle, leading to pathological changes of the articular joint in obese individuals. This review addresses obesity and the role of all the immune cells that are involved in OA and summarised animal studies and human trials and knowledge gaps between the studies have been highlighted. The review also touches base on the interventions currently in clinical trials, different stages of the testing, and their shortcomings are also discussed to understand the future direction which could help in understanding the multifactorial aspects of OA where inflammation has a significant function.

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Section: Anti-inflammatory Therapeutics For Oamentioning

confidence: 84%

Obesity, Inflammation, and Immune System in Osteoarthritis

et al. 2022

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“…We found that hyaluronan therapy increased anti-fibrotic macrophages and decreased pain sensitization, while treatment with MSCs did not impact pain, but led to long-term chondroprotection ( 300 ). Along similar lines, another recent study demonstrated that administration of Alpha defensin-1 renders macrophages less inflammatory and attenuates OA in a surgical model ( 301 ). Collectively, these data suggest that specific anti-inflammatory treatment immediately after knee injury might represent a promising future therapeutic approach, and thus, justify additional experimental and ultimately clinical studies.…”

Section: Harnessing Monocyte and Macrophage Biology For Oa Risk Stratification Diagnosis And Therapy?mentioning

confidence: 72%

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

et al. 2021

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Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: “a macrophage niche”. These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

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“…Since more and more researches have uncovered the importance of macrophages in OA [ 13 , 36 , 37 ], we wondered whether CDs we synthesized regulated OA progression through immunoregulatory effect. It was shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages

Zhang

Qin

et al. 2022

J Nanobiotechnol

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Background Osteoarthritis (OA) is a common joint disorder worldwide which causes great health and economic burden. However, there remains an unmet goal to develop an effective therapeutic method to prevent or delay OA. Chondrocytes, as the major cells involved in OA progression, may serve as a promising therapeutic target. Results A kind of carbon dots (CDs) with excellent biocompatibility was fabricated from folic acid via hydrothermal method and could effectively attenuate osteoarthritis. It was demonstrated that CDs treatment could rescue IL1β-induced proinflammatory responses, oxidative stress, cartilage degeneration and extracellular matrix degradation. Moreover, CDs reprogrammed lipopolysaccharide (LPS)-induced macrophage inflammation and polarization. Conditioned medium (CM) from CDs-treated macrophages could attenuate IL1β-induced chondrocyte injury. Also, CM from CDs-treated chondrocytes had immunoregulatory functions on macrophages. Mechanistically, CDs inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in IL1β-stimulated chondrocytes. In vivo, anterior cruciate ligament transection (ACLT) mice model was adopted and it was indicated that intra-articular injection of CDs effectively delays OA pathogenesis. Conclusions Taken together, these findings indicated CDs could mediate OA via promoting cartilage repair and immunomodulating macrophages within local microenvironment, which may provide evidences for utilizing CDs as a novel nanomaterial for OA treatment.

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Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization

Cited by 25 publications

References 50 publications

Obesity, Inflammation, and Immune System in Osteoarthritis

Obesity, Inflammation, and Immune System in Osteoarthritis

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages

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