Superstable lipid vacuoles endow cartilage with its shape and biomechanics

• Published in: Science (American Association for the Advancement of Science) 2025-01, Vol.387 (6730), p.eads9960
• Main Authors: Ramos, Raul, Pham, Kim T, Prince, Richard C, Leiser-Miller, Leith B, Prasad, Maneeshi S, Wang, Xiaojie, Nordberg, Rachel C, Bielajew, Benjamin J, Hu, Jerry C, Yamaga, Kosuke, Oh, Ji Won, Peng, Tao, Datta, Rupsa, Astrowskaja, Aksana, Almet, Axel A, Burns, John T, Liu, Yuchen, Guerrero-Juarez, Christian Fernando, Tran, Bryant Q, Chu, Yi-Lin, Nguyen, Anh M, Hsi, Tsai-Ching, Lim, Norman T-L, Schoeniger, Sandra, Liu, Ruiqi, Pai, Yun-Ling, Vadivel, Chella K, Ingleby, Sandy, McKechnie, Andrew E, van Breukelen, Frank, Hoehn, Kyle L, Rasweiler, 4th, John J, Kohara, Michinori, Loughry, William J, Weldy, Scott H, Cosper, Raymond, Yang, Chao-Chun, Lin, Sung-Jan, Cooper, Kimberly L, Santana, Sharlene E, Bradley, Jeffrey E, Kiebish, Michael A, Digman, Michelle, James, David E, Merrill, Amy E, Nie, Qing, Schilling, Thomas F, Astrowski, Aliaksandr A, Potma, Eric O, García-Castro, Martín I, Athanasiou, Kyriacos A, Behringer, Richard R, Plikus, Maksim V
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipose tissue; Animals; Bats; Biomarkers; Biomechanical Phenomena; Biomechanics; Bones; Cartilage; Cartilage - anatomy & histology; Cartilage - physiology; Cell differentiation; Cell size; Chest; Dietary restrictions; Ear; Echolocation; Elastic properties; Embryo cells; Embryogenesis; Embryology; Embryonic growth stage; Enzymes; Extracellular matrix; Extracellular Matrix - metabolism; Fatty acids; Gene expression; Genes; Genetic markers; Humans; Hydrostatics; Individualized Instruction; Intervertebral discs; Larynx; Lipid Droplets - metabolism; Lipid Metabolism; Lipids; Lipogenesis; Mammals; Mechanical properties; Metabolism; Mice; Micropatterning; Notochord; Obesity - metabolism; Phylogeny; Pluripotency; Precursors; Progenitor cells; Regenerative medicine; Stem cells; Tissue engineering; Transcription factors; Vacuoles - metabolism; Vertebrates
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.ads9960

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.