Superstable lipid vacuoles endow cartilage with its shape and biomechanics
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.
Authors
- Kyriacos A. Athanasiou (ORCID: https://orcid.org/0000-0001-5387-8405)
- Justin M. Burns (ORCID: https://orcid.org/0000-0002-4628-8535)
- Yi-Lin Chu
- Raúl Ramos (ORCID: https://orcid.org/0000-0003-0853-1028)
- Michael A. Kiebish (ORCID: https://orcid.org/0000-0002-5678-0072)
- Kyle L. Hoehn (ORCID: https://orcid.org/0000-0002-0214-3238)
- Rachel C. Nordberg (ORCID: https://orcid.org/0000-0001-6047-6009)
- Richard C. Prince (ORCID: https://orcid.org/0000-0003-1199-9465)
- David Ernest James (ORCID: https://orcid.org/0000-0001-5946-5257)
- Martín I. García‐Castro (ORCID: https://orcid.org/0000-0001-5128-0004)
- Michinori Kohara (ORCID: https://orcid.org/0000-0002-2130-5837)
- Michelle A. Digman (ORCID: https://orcid.org/0000-0003-4611-7100)
- Tao Peng (ORCID: https://orcid.org/0000-0002-5779-3377)
- Andrew E. McKechnie (ORCID: https://orcid.org/0000-0002-1524-1021)
- A. B. Astrowskaja (ORCID: https://orcid.org/0000-0003-3513-2014)
- Jeffrey E. Bradley (ORCID: https://orcid.org/0000-0001-7390-2978)
- Thomas F. Schilling (ORCID: https://orcid.org/0000-0003-1798-8695)
- Y. Liu
- Axel A. Almet (ORCID: https://orcid.org/0000-0001-9173-8278)
- Ji Won Oh (ORCID: https://orcid.org/0000-0001-5742-5120)
- Christian F. Guerrero‐Juarez (ORCID: https://orcid.org/0000-0002-6245-6412)
- Amy Elizabeth Merrill (ORCID: https://orcid.org/0000-0002-3660-1575)
- Maneeshi S. Prasad (ORCID: https://orcid.org/0000-0003-0813-4153)
- Benjamin J. Bielajew (ORCID: https://orcid.org/0000-0003-0580-9864)
- Sung‐Jan Lin (ORCID: https://orcid.org/0000-0003-1325-3464)
- Norman T.‐L. Lim (ORCID: https://orcid.org/0000-0001-7350-6975)
- John J. Rasweiler (ORCID: https://orcid.org/0000-0002-6049-2372)
- Maksim V. Plikus (ORCID: https://orcid.org/0000-0002-8845-2559)
- Frank van Breukelen (ORCID: https://orcid.org/0000-0001-9653-0273)
- Eric O. Potma (ORCID: https://orcid.org/0000-0003-3916-6131)
- Sharlene E. Santana (ORCID: https://orcid.org/0000-0001-6463-3569)
- Chella Krishna Vadivel (ORCID: https://orcid.org/0000-0002-3710-5143)
- Tsai‐Ching Hsi (ORCID: https://orcid.org/0000-0001-8812-3133)
- Kimberly L. Cooper (ORCID: https://orcid.org/0000-0001-5892-8838)
- Qing Nie (ORCID: https://orcid.org/0000-0002-8804-3368)
- Sandra Schöniger (ORCID: https://orcid.org/0000-0002-6742-011X)
- W. J. Loughry (ORCID: https://orcid.org/0000-0001-8214-9893)
- Chao‐Chun Yang (ORCID: https://orcid.org/0000-0002-3897-6522)
- Richard R. Behringer (ORCID: https://orcid.org/0000-0001-7282-1543)
- Jerry C. Hu (ORCID: https://orcid.org/0000-0003-0651-1461)
- Rupsa Datta (ORCID: https://orcid.org/0000-0002-6432-2389)
- Kosuke Yamaga
- A. A. Astrowski (ORCID: https://orcid.org/0000-0001-8647-3922)
- Xiaojie Wang (ORCID: https://orcid.org/0000-0003-4817-5830)
- Ruiqi Liu (ORCID: https://orcid.org/0000-0002-2099-620X)
- A. Nguyen (ORCID: https://orcid.org/0000-0003-4301-013X)
- Y.P. Pai
- Bryant Q. Tran
- Kim T. Pham
- Sandy Ingleby
- Scott H. Weldy
- Raymond Cosper
- Leith B. Leiser-Miller
Institutions
- Valdosta State University (US)
- University of California, Riverside (US)
- University of Southern California (US)
- University of Copenhagen (DK)
- The University of Sydney (AU)
- Australian Museum (AU)
- University of Nevada, Las Vegas (US)
- The University of Texas MD Anderson Cancer Center (US)
- National Taiwan University (TW)
- SUNY Downstate Health Sciences University (US)
- Yonsei University (KR)
- University of Washington (US)
- University of California, Irvine (US)
- Kyungpook National University Hospital (KR)
- Kyungpook National University (KR)
- UNSW Sydney (AU)
- University of California San Diego (US)
- South African National Biodiversity Institute (ZA)
- Associated Research (United States) (US)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Burke Museum of Natural History and Culture (US)
- International Data Group (United States) (US)
- LEO Foundation (DK)
- Grodno State Medical University (BY)
- Institute of Biochemistry of Biologically Active Compounds of the National Academy of Sciences of Belarus (BY)
- National Cheng Kung University Hospital (TW)
- Framingham State University (US)
- University at Buffalo, State University of New York (US)
- University of Pretoria (ZA)
- Santa Ana College (US)
- National Cheng Kung University (TW)
- Leipzig University (DE)
Publication Details
- Journal
- Science
- Published
- 2025-01-09
- DOI
- https://doi.org/10.1126/science.ads9960
- Citations
- 20
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 16.12
Funders
- National Science Foundation
- W. M. Keck Foundation
- Yoshida Scholarship Foundation
- LEO Fondet
- National Institutes of Health
- University of California, Riverside
- HORIZON EUROPE Framework Programme
- Division of Chemical, Bioengineering, Environmental, and Transport Systems