无细胞脂肪提取物通过抑制ATF3结合染色质可及性来减轻颞下颌关节骨性关节炎
Cell-free fat extract attenuates temporomandibular joint osteoarthritis via repressing ATF3-binding chromatin accessibility.
摘要(中文译文)
颞下颌关节骨关节炎（TMJOA）是一种以软骨退变和滑膜炎症为特征的退行性疾病，治疗选择有限。在本研究中，我们评估了无细胞脂肪提取物（CEFFE）——一种来源于脂肪组织的生物活性组分——作为TMJOA治疗策略的潜力。在软骨细胞中，CEFFE促进增殖和活力，减轻炎症性凋亡，并通过上调Col2a1和Sox9、抑制基质金属蛋白酶来维持细胞外基质稳态。整合转录组学和表观基因组学分析表明，CEFFE通过抑制ATF3结合染色质可及性，减少活化转录因子3（ATF3）在肌动蛋白结合LIM蛋白1（ABLIM1）启动子区域的结合，从而抑制核因子κB（NF-κB）信号通路。在TMJOA大鼠模型中，关节腔内注射CEFFE可减轻软骨退变、软骨下骨丢失和滑膜炎，且无全身毒性。CEFFE还抑制促炎性M1巨噬细胞极化，并降低滑膜组织中白细胞介素-1β和肿瘤坏死因子-α的表达。这些发现表明，CEFFE是一种双靶点治疗剂，通过表观遗传调控ATF3/ABLIM1/NF-κB信号通路同时调节软骨细胞和巨噬细胞。我们的研究凸显了CEFFE作为一种安全且可及的生物材料，具有作为TMJOA再生和抗炎策略进行临床转化的潜力。
Abstract
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by cartilage degradation and synovial inflammation with limited therapeutic options. In our study, cell-free fat extract (CEFFE), a bioactive fraction derived from adipose tissue, is evaluated as a therapeutic strategy for TMJOA. In chondrocytes, CEFFE enhances proliferation and viability, attenuates inflammatory apoptosis, and preserves extracellular matrix homeostasis by upregulating Col2a1 and Sox9 while suppressing matrix metalloproteinases. Integrated transcriptomic and epigenomic analyses demonstrate that CEFFE reduces the activating transcription factor 3 (ATF3) binding at the promoter of actin binding LIM protein 1 (ABLIM1) via repressing ATF3-binding chromatin accessibility, thereby inhibiting nuclear factor kappa-B (NF-κB) signaling. In a rat model of TMJOA, intra-articular administration of CEFFE alleviates cartilage degeneration, subchondral bone loss, and synovitis, without systemic toxicity. CEFFE also suppresses pro-inflammatory M1 macrophage polarization and decreases interleukin-1β and tumor necrosis factor-α expression in synovial tissue. These findings identify CEFFE as a dual-target therapeutic agent that modulates both chondrocytes and macrophages through epigenetic regulation of ATF3/ABLIM1/NF-κB signaling. Our study highlights CEFFE as a safe and accessible biomaterial with potential for clinical translation as a regenerative and anti-inflammatory strategy for TMJOA.
如何引用
AMA
Dahe Zhang, Bijun Kang, Shaonan Wan, Xiaohan Liu, Simo Xia, Yuxin Zhang, et al. Cell-free fat extract attenuates temporomandibular joint osteoarthritis via repressing ATF3-binding chromatin accessibility.. Biomaterials. 2026; doi:10.1016/j.biomaterials.2026.124091.
APA
Dahe Zhang, Bijun Kang, Shaonan Wan, Xiaohan Liu, Simo Xia, Yuxin Zhang, et al (2026). Cell-free fat extract attenuates temporomandibular joint osteoarthritis via repressing ATF3-binding chromatin accessibility.. Biomaterials. https://doi.org/10.1016/j.biomaterials.2026.124091
GB/T 7714
Dahe Zhang, Bijun Kang, Shaonan Wan, Xiaohan Liu, Simo Xia, Yuxin Zhang, et al. Cell-free fat extract attenuates temporomandibular joint osteoarthritis via repressing ATF3-binding chromatin accessibility.[J]. Biomaterials, 2026 doi:10.1016/j.biomaterials.2026.124091.
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