Superstable lipid vacuoles endow cartilage with its shape and biomechanics

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2025-01-09 DOI:10.1126/science.ads9960

Raul Ramos, Kim T. Pham, Richard C. Prince, Leith B. Leiser-Miller, Maneeshi S. Prasad, Xiaojie Wang, Rachel C. Nordberg, Benjamin J. Bielajew, Jerry C. Hu, Kosuke Yamaga, Ji Won Oh, Tao Peng, Rupsa Datta, Aksana Astrowskaja, Axel A. Almet, John T. Burns, Yuchen Liu, Christian Fernando Guerrero-Juarez, Bryant Q. Tran, Yi-Lin Chu, Anh M. Nguyen, Tsai-Ching Hsi, Norman T.-L. Lim, Sandra Schoeniger, Ruiqi Liu, Yun-Ling Pai, Chella K. Vadivel, Sandy Ingleby, Andrew E. McKechnie, Frank van Breukelen, Kyle L. Hoehn, John J. Rasweiler, Michinori Kohara, William J. Loughry, Scott H. Weldy, Raymond Cosper, Chao-Chun Yang, Sung-Jan Lin, Kimberly L. Cooper, Sharlene E. Santana, Jeffrey E. Bradley, Michael A. Kiebish, Michelle Digman, David E. James, Amy E. Merrill, Qing Nie, Thomas F. Schilling, Aliaksandr A. Astrowski, Eric O. Potma, Martín I. García-Castro, Kyriacos A. Athanasiou, Richard R. Behringer, Maksim V. Plikus

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Abstract

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue’s stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without “packing foam–like” extracellular matrix.

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超稳定脂泡赋予软骨形态和生物力学

通常，软骨的大小、形状和生物力学是由其体积的细胞外基质决定的。相比之下，我们发现多种小鼠软骨由称为脂质软骨细胞的充脂细胞组成。尽管与脂肪细胞相似，但脂质软骨细胞在分子上是不同的，并且完全通过新生脂肪生成来产生脂质。因此，脂质软骨细胞形成均匀的脂滴，抵抗全身脂质激增，并且不会随着肥胖而扩大。脂质软骨细胞也缺乏脂质动员因子，这使得液泡异常稳定，并保护软骨在饥饿时不萎缩。脂滴通过降低组织的硬度、强度和弹性来调节脂软骨的生物力学。脂质软骨细胞存在于包括人类在内的多种哺乳动物中，但未在非哺乳动物四足动物中发现。因此，与气泡膜类似，超稳定的脂质液泡使骨组织具有软骨样特性，而不需要“填充泡沫样”细胞外基质。

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Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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