Tunnelling Nanotube-Mediated Lysosome Sharing Promotes Osteocyte Survival via Transcellular Autophagy

Jinbiao Qiang , Ronghao Jin , Tong Sha , Fang Zheng , Yijun Zhou , Yue Hu , Shuyu Zhang , Zhenming Yang , Mengdong Nie , Huanyu Luo , Xiaoduo Tang , Hao Guo , Zunxuan Xie , Jinwei Li , Hongchen Sun , Cangwei Liu , Ce Shi

Cell Proliferation ›› 2026, Vol. 59 ›› Issue (7) : e70226

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Cell Proliferation ›› 2026, Vol. 59 ›› Issue (7) :e70226 DOI: 10.1111/cpr.70226
ORIGINAL ARTICLE
Tunnelling Nanotube-Mediated Lysosome Sharing Promotes Osteocyte Survival via Transcellular Autophagy
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Abstract

Osteocytes, the central regulators of bone remodelling, are essential for maintaining bone homeostasis. Embedded in a nutrient-limited matrix and burdened by cumulative stress over their exceptionally long lifespan, how osteocytes sustain long-term viability remains elusive. Tunnelling nanotubes (TNTs) are newly described intercellular bridges that enable long-range transfer of organelles and have been implicated in stress adaptation. Here, we provide the first definitive identification of TNTs between cultured osteocytes, which exhibit canonical TNT morphology together with osteocyte-specific features. Functionally, osteocytic TNTs mediate intercellular transfer of membrane-bound cargo, predominantly lysosomes. Under nutrient deprivation, TNT formation and lysosome transfer are both increased, replenishing the lysosomal pool in stressed osteocytes. Transferred lysosomes then fuse with accumulated autophagosomes, thereby restoring impaired autophagic flux and suppressing apoptosis. This cytoprotective effect requires TNT integrity and intact autophagic flux. Although mitochondrial transfer is detectable, it does not confer comparable protection. The findings identify a transcellular autophagy pathway mediated by TNT-dependent lysosome sharing, revealing a previously unrecognized cooperative survival strategy among osteocytes. This work establishes a novel conceptual framework in osteocyte biology and suggests potential therapeutic avenues for bone diseases associated with osteocyte apoptosis and impaired bone remodelling.

Keywords

apoptosis / intercellular communication / lysosomes / mitochondria / osteocytes / transcellular autophagy / tunnelling nanotubes

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Jinbiao Qiang, Ronghao Jin, Tong Sha, Fang Zheng, Yijun Zhou, Yue Hu, Shuyu Zhang, Zhenming Yang, Mengdong Nie, Huanyu Luo, Xiaoduo Tang, Hao Guo, Zunxuan Xie, Jinwei Li, Hongchen Sun, Cangwei Liu, Ce Shi. Tunnelling Nanotube-Mediated Lysosome Sharing Promotes Osteocyte Survival via Transcellular Autophagy. Cell Proliferation, 2026, 59 (7) : e70226 DOI:10.1111/cpr.70226

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