中文摘要：

巨噬細胞參與骨關節炎（OA）的發病機制，但特定巨噬細胞狀態如何影響軟骨細胞衰老仍不清楚。通過對自然衰老小鼠關節進行單細胞RNA測序，我們鑒定出一個與關節衰老相關的PTGS2高表達巨噬細胞亞群。在手術誘導的OA模型中，譜系追蹤顯示這些巨噬細胞顯著增加，而利用基于白喉毒素受體的小鼠模型選擇性清除這些細胞可減輕軟骨衰老和疾病進展。PTGS2+巨噬細胞來源的THBS1通過SDC4相關的細胞周相互作用，并至少部分通過TGF-β依賴性信號通路，促進軟骨細胞衰老。巨噬細胞特異性敲除Thbs1可減少軟骨細胞衰老標志物并減輕OA樣退變。在機制上，糖酵解產生的乳酸升高增強了THBS1在賴氨酸262（K262）位點的乳?；?，從而減少NEDD4依賴性泛素化并穩定THBS1蛋白。關節內靶向PTGS2高表達巨噬細胞可減輕軟骨細胞衰老和OA進展。這些發現將巨噬細胞代謝重編程與促衰老分泌途徑聯系起來，并為OA提出了一種局部遞送策略。

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.

論文信息：

論文題目：Targeting pro-senescent PTGS2+ macrophages alleviates chondrocyte senescence and osteoarthritis progression

期刊名稱：Cell Reports

時間期卷：Volume 45, Issue 9117907

DOI: 10.1016/j.celrep.2026.117907

產品信息：

貨號：CP-005-005

規格：5ml+5ml

品牌：Liposoma

產地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質體清除骨關節炎（OA）小鼠巨噬細胞荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Cell Reports：靶向促衰老的PTGS2+巨噬細胞可減輕軟骨細胞衰老和骨關節炎進展。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法：

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.

巨噬細胞清除材料和方法文獻截圖：