Dataset Information

NLRP3-Dependent Crosstalk between Pyroptotic Macrophage and Senescent Cell Orchestrates Trauma-Induced Heterotopic Ossification During Aberrant Wound Healing.

ABSTRACT: Heterotopic ossification (HO) represents an unwanted ossific wound healing response to the soft tissue injury which caused catastrophic limb dysfunction. Recent studies established the involvement of inflammation and cellular senescence in the tissue healing process, though their role in HO still remained to be clarified. Here, a novel crosstalk where the pyroptotic macrophages aroused tendon-derived stem cells (TDSCs) senescence is revealed to encourage osteogenic healing during trauma-induced HO formation. Macrophage pyroptosis blockade reduces the senescent cell burden and HO formation in NLRP3 knockout mice. Pyroptosis-driven IL-1β and extracellular vesicles (EVs) secretion from macrophages are determined to motivate TDSCs senescence and resultant osteogenesis. Mechanistically, pyroptosis in macrophages enhances the exosomal release of high mobility group protein 1 (HMGB1), which directly bounds TLR9 in TDSCs to trigger morbid signaling. NF-κB signaling is confirmed to be the converging downstream pathway of TDSCs in response to HMGB1-containing EVs and IL-1β. This study adds insights into aberrant regeneration-based theory for HO formation and boosts therapeutic strategy development.

SUBMITTER: Li J

PROVIDER: S-EPMC10323626 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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NLRP3-Dependent Crosstalk between Pyroptotic Macrophage and Senescent Cell Orchestrates Trauma-Induced Heterotopic Ossification During Aberrant Wound Healing.

Li Juehong J Wang Xin X Yao Zhixiao Z Yuan Feng F Liu Hang H Sun Zhenyu Z Yuan Zhengqiang Z Luo Gang G Yao Xiangyun X Cui Haomin H Tu Bing B Sun Ziyang Z Fan Cunyi C

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20230519 19

Heterotopic ossification (HO) represents an unwanted ossific wound healing response to the soft tissue injury which caused catastrophic limb dysfunction. Recent studies established the involvement of inflammation and cellular senescence in the tissue healing process, though their role in HO still remained to be clarified. Here, a novel crosstalk where the pyroptotic macrophages aroused tendon-derived stem cells (TDSCs) senescence is revealed to encourage osteogenic healing during trauma-induced ...[more]

PMID: 37204068

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Project description:Heterotopic Ossification (HO) is a potential long-term complication in orthopaedic surgery. It is commonly classified according to the Brooker classification, which is based on radiological findings. To our knowledge the correlation of histological features to the Brooker grade is unknown as is the association between HO and the indication for revision. The aim of this paper is to analyze the ossification grade of HO tissue in patients undergoing revision hip and knee arthroplasty and to propose a histologically based classification system for HO. We also assess the relationship between the grade of HO and the indication for revision (septic and aseptic revision). From January to May 2019 we collected 50 human HO samples from hip and knee revision arthroplasty cases. These tissue samples were double-blinded and sent for histopathological diagnostic. Based on these results, we developed a classification system for the progression of HO. The grade of ossification was based on three characteristics: Grade of heterotopic ossification (Grade 1-3), presence of necrosis (N0 or N1) and the presence of osteomyelitis (HOES-Score Type 1 to 5). Demographic data as well as surgical details and indication for surgery was prospectively collected from clinical records. Fifty tissue samples were harvested from 44 hips and 6 knee joints. Of these 33 exhibited Grade I ossifications (66%), followed by 11 Grade II (22%) and one Grade III (2%). Necrosis was noted in two tissue samples (4%) and 2 more had osteomyelitis findings according to HOES-Score. Six samples (12%) with radiologically suggestive of HO turned out to be wear-induced synovitis, SLIM Type 1. Of these cases 16 were septic (32%) and 34 aseptic (68%) revisions. Most of the HO tissue samples were classified as a low-grade. High-grade ossification-Score is rare. Higher grades of ossification seem to be associated with septic revision cases. Wear-induced synovitis potentially influences HO development. A histological scoring system for ossification grading can be derived from the data presented in this study.

Dataset Information

NLRP3-Dependent Crosstalk between Pyroptotic Macrophage and Senescent Cell Orchestrates Trauma-Induced Heterotopic Ossification During Aberrant Wound Healing.

Publications

NLRP3-Dependent Crosstalk between Pyroptotic Macrophage and Senescent Cell Orchestrates Trauma-Induced Heterotopic Ossification During Aberrant Wound Healing.

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