Superstable lipid vacuoles endow cartilage with its shape and biomechanics

Raul Ramos^{1

2}, Kim T Pham^{1

2}, Richard C Prince^{3

4}, Leith B Leiser-Miller⁵, Maneeshi S Prasad^{6

7}, Xiaojie Wang^{1

2}, Rachel C Nordberg⁴, Benjamin J Bielajew⁴, Jerry C Hu⁴, Kosuke Yamaga^{1

2}, Ji Won Oh^{1

2

8

9

10}, Tao Peng^{11

12}, Rupsa Datta⁴, Aksana Astrowskaja¹³, Axel A Almet^{11

14}, John T Burns^{1

2}, Yuchen Liu^{1

2}, Christian Fernando Guerrero-Juarez^{1

2

11

12}, Bryant Q Tran^{1

2}, Yi-Lin Chu^{1

2}, Anh M Nguyen^{1

2}, Tsai-Ching Hsi^{1

2}, Norman T-L Lim¹⁵, Sandra Schoeniger^{16

17}, Ruiqi Liu^{1

2}, Yun-Ling Pai^{2

18}, Chella K Vadivel^{2

19}, Sandy Ingleby²⁰, Andrew E McKechnie^{21

22}, Frank van Breukelen²³, Kyle L Hoehn²⁴, John J Rasweiler 4th²⁵, Michinori Kohara²⁶, William J Loughry²⁷, Scott H Weldy²⁸, Raymond Cosper²⁹, Chao-Chun Yang^{30

31}, Sung-Jan Lin¹⁸, Kimberly L Cooper³², Sharlene E Santana^{5

33}, Jeffrey E Bradley³³, Michael A Kiebish³⁴, Michelle Digman^{12

35}, David E James³⁶, Amy E Merrill³⁷, Qing Nie^{11

12

14}, Thomas F Schilling^{1

12

14}, Aliaksandr A Astrowski³⁸, Eric O Potma³, Martín I García-Castro⁶, Kyriacos A Athanasiou⁴, Richard R Behringer³⁹, Maksim V Plikus^{1

2

12

14}

Affiliations

¹ Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
² Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
³ Department of Chemistry, University of California, Irvine, Irvine, CA, USA.
⁴ Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA.
⁵ Department of Biology, University of Washington, Seattle, WA, USA.
⁶ Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USA.
⁷ Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
⁸ Department of Anatomy, College of Medicine, Yonsei University, Seoul, Republic of Korea.
⁹ Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
¹⁰ Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea.
¹¹ Department of Mathematics, University of California, Irvine, Irvine, CA, USA.
¹² Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA.
¹³ Scientific Research Laboratory of Molecular Medicine, Grodna State Medical University, Grodna, Belarus.
¹⁴ NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA, USA.
¹⁵ National Institute of Education, Singapore, Republic of Singapore.
¹⁶ Institute of Veterinary Pathology, Leipzig University, Leipzig, Germany.
¹⁷ Discovery Life Sciences Biomarker Services GmbH, Kassel, Germany.
¹⁸ Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
¹⁹ LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
²⁰ Australian Museum, Sydney, NSW, Australia.
²¹ Mammal Research Institute, Department of Zoology and Entomology, University of Pretoria, Hatfield, South Africa.
²² South African National Biodiversity Institute, Pretoria, South Africa.
²³ School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA.
²⁴ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
²⁵ Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, New York, NY, USA.
²⁶ Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
²⁷ Valdosta State University, Valdosta, GA, USA.
²⁸ Serrano Animal and Bird Hospital, Lake Forest, CA, USA.
²⁹ Santa Ana Zoo, Santa Ana, CA, USA.
³⁰ Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³¹ International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan.
³² Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA.
³³ Department of Mammalogy, Burke Museum, University of Washington, Seattle, WA, USA.
³⁴ BPGbio, Inc., Framingham, MA, USA.
³⁵ Department of Chemical Engineering and Materials Science, University of California, Irvine, Irvine, CA, USA.
³⁶ Charles Perkins Centre, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
³⁷ Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
³⁸ The Institute of Biochemistry of Biologically Active Compounds, Grodna, Belarus.
³⁹ Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

PMID: 39787221
PMCID: PMC12279017 (available on 2026-01-10)
DOI: 10.1126/science.ads9960

Superstable lipid vacuoles endow cartilage with its shape and biomechanics

Raul Ramos et al. Science. 2025.

. 2025 Jan 10;387(6730):eads9960.

doi: 10.1126/science.ads9960. Epub 2025 Jan 10.

Authors

Affiliations

¹ Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
² Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
³ Department of Chemistry, University of California, Irvine, Irvine, CA, USA.
⁴ Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA.
⁵ Department of Biology, University of Washington, Seattle, WA, USA.
⁶ Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USA.
⁷ Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
⁸ Department of Anatomy, College of Medicine, Yonsei University, Seoul, Republic of Korea.
⁹ Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
¹⁰ Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea.
¹¹ Department of Mathematics, University of California, Irvine, Irvine, CA, USA.
¹² Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA.
¹³ Scientific Research Laboratory of Molecular Medicine, Grodna State Medical University, Grodna, Belarus.
¹⁴ NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA, USA.
¹⁵ National Institute of Education, Singapore, Republic of Singapore.
¹⁶ Institute of Veterinary Pathology, Leipzig University, Leipzig, Germany.
¹⁷ Discovery Life Sciences Biomarker Services GmbH, Kassel, Germany.
¹⁸ Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
¹⁹ LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
²⁰ Australian Museum, Sydney, NSW, Australia.
²¹ Mammal Research Institute, Department of Zoology and Entomology, University of Pretoria, Hatfield, South Africa.
²² South African National Biodiversity Institute, Pretoria, South Africa.
²³ School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA.
²⁴ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
²⁵ Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, New York, NY, USA.
²⁶ Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
²⁷ Valdosta State University, Valdosta, GA, USA.
²⁸ Serrano Animal and Bird Hospital, Lake Forest, CA, USA.
²⁹ Santa Ana Zoo, Santa Ana, CA, USA.
³⁰ Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³¹ International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan.
³² Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA.
³³ Department of Mammalogy, Burke Museum, University of Washington, Seattle, WA, USA.
³⁴ BPGbio, Inc., Framingham, MA, USA.
³⁵ Department of Chemical Engineering and Materials Science, University of California, Irvine, Irvine, CA, USA.
³⁶ Charles Perkins Centre, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
³⁷ Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
³⁸ The Institute of Biochemistry of Biologically Active Compounds, Grodna, Belarus.
³⁹ Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

PMID: 39787221
PMCID: PMC12279017 (available on 2026-01-10)
DOI: 10.1126/science.ads9960

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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Conflict of interest statement

Competing Interests: R.R. and M.V.P. are co-inventors on a patent application filed by the Regents of the University of California describing the method for producing and purifying human stem cell-derived cartilage cells on the basis of lipid vacuoles, among other claims. K.A.A. and J.C.H are co-founders of Cartilage Inc. R.C.P. is also affiliated with East Tennessee State University. R.D. is also affiliated with Morgridge Institute for Research.

Comment in

A long-ignored skeletal tissue filled with oil.
Aguayo VH, Selleri L. Aguayo VH, et al. Science. 2025 Jan 10;387(6730):136-137. doi: 10.1126/science.adu7943. Epub 2025 Jan 9. Science. 2025. PMID: 39787246

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Superstable lipid vacuoles endow cartilage with its shape and biomechanics

Affiliations

Superstable lipid vacuoles endow cartilage with its shape and biomechanics

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Molecular Biology Databases