中文摘要：
巨噬细胞参与骨关节炎（OA）的发病机制，但特定巨噬细胞状态如何影响软骨细胞衰老仍不清楚。通过对自然衰老小鼠关节进行单细胞RNA测序，我们鉴定出一个与关节衰老相关的PTGS2高表达巨噬细胞亚群。在手术诱导的OA模型中，谱系追踪显示这些巨噬细胞显著增加，而利用基于白喉毒素受体的小鼠模型选择性清除这些细胞可减轻软骨衰老和疾病进展。PTGS2+巨噬细胞来源的THBS1通过SDC4相关的细胞周相互作用，并至少部分通过TGF-β依赖性信号通路，促进软骨细胞衰老。巨噬细胞特异性敲除Thbs1可减少软骨细胞衰老标志物并减轻OA样退变。在机制上，糖酵解产生的乳酸升高增强了THBS1在赖氨酸262（K262）位点的乳酰化，从而减少NEDD4依赖性泛素化并稳定THBS1蛋白。关节内靶向PTGS2高表达巨噬细胞可减轻软骨细胞衰老和OA进展。这些发现将巨噬细胞代谢重编程与促衰老分泌途径联系起来，并为OA提出了一种局部递送策略。
英文摘要：
Macrophages contribute to osteoarthritis (OA) pathogenesis, but how specific macrophage states influence chondrocyte senescence remains unclear. Using single-cell RNA sequencing of naturally aged mouse joints, we identified a PTGS2-high macrophage subset associated with joint senescence. In a surgically induced OA model, lineage tracing revealed a marked increase of these macrophages, and their selective depletion using a diphtheria toxin receptor-based mouse model attenuated cartilage senescence and disease progression. PTGS2+ macrophage-derived THBS1 promoted chondrocyte senescence through SDC4-associated pericellular interactions and, at least in part, TGF-β-dependent signaling. Macrophage-specific deletion of Thbs1 reduced chondrocyte senescence markers and attenuated OA-like degeneration. Mechanistically, elevated glycolytic lactate enhanced THBS1 lactylation at lysine 262 (K262), which reduces NEDD4-dependent ubiquitination and stabilizes THBS1 protein. Intra-articular targeting of PTGS2-high macrophages attenuated chondrocyte senescence and OA progression. These findings link macrophage metabolic remodeling to a pro-senescent secreted pathway and suggest a locally delivered strategy for OA.
论文信息：
论文题目：Targeting pro-senescent PTGS2+ macrophages alleviates chondrocyte senescence and osteoarthritis progression
期刊名称：Cell Reports
时间期卷：Volume 45, Issue 9117907
DOI: 10.1016/j.celrep.2026.117907
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除骨关节炎（OA）小鼠巨噬细胞荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Cell Reports：靶向促衰老的PTGS2+巨噬细胞可减轻软骨细胞衰老和骨关节炎进展。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
DMM surgery and in vivo interventions
For DMM surgery, mice were anesthetized with 1.5%–2.0% isoflurane in oxygen and placed on a heating pad. After skin disinfection, the right knee joint was exposed through a medial parapatellar incision, and the medial meniscotibial ligament was transected under a stereomicroscope to destabilize the medial meniscus. Sham-operated mice underwent joint-capsule exposure without ligament transection. Postoperative analgesia was provided with buprenorphine (0.05 mg/kg, subcutaneously) every 12 h for 48 h. For inducible recombination, tamoxifen was dissolved in corn oil and administered intraperitoneally at 100 mg/kg once daily for 5 consecutive days; DMM or sham surgery was performed 7 days after the final tamoxifen injection unless otherwise indicated in the figure scheme. For inducible depletion in Ptgs2-P2A-CreERT2;Cd68-LSL-DTR mice (shown as Ptgs2-CreERT2;Cd68-LSL-DTR in Figure 2C), diphtheria toxin was administered intraperitoneally at 50 μg/kg according to the timeline in Figure 2C. For global synovial macrophage depletion, clodronate liposomes or control liposomes were injected intra-articularly at 10 μL per knee according to the experimental timeline.
巨噬细胞清除材料和方法文献截图：
