Superstable lipid vacuoles endow cartilage with its shape and biomechanics

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

doi:10.1126/science.ads9960

Superstable lipid vacuoles endow cartilage with its shape and biomechanics

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 ChuAnh 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

皮膚學科

研究成果: Article › 同行評審

3 引文斯高帕斯（Scopus）

摘要

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.

原文	English
頁（從 - 到）	eads9960
期刊	Science
卷	387
發行號	6730
DOIs	https://doi.org/10.1126/science.ads9960
出版狀態	Published - 2025 1月 10

All Science Journal Classification (ASJC) codes

多學科

UN SDG

此研究成果有助於以下永續發展目標

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10.1126/science.ads9960

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引用此

Ramos, R., Pham, K. T., Prince, R. C., Leiser-Miller, L. B., Prasad, M. S., Wang, X., Nordberg, R. C., Bielajew, B. J., Hu, J. C., Yamaga, K., Oh, J. W., Peng, T., Datta, R., Astrowskaja, A., Almet, A. A., Burns, J. T., Liu, Y., Guerrero-Juarez, C. F., Tran, B. Q., ... Plikus, M. V. (2025). Superstable lipid vacuoles endow cartilage with its shape and biomechanics. Science, 387(6730), eads9960. https://doi.org/10.1126/science.ads9960

@article{02ab12bb7be34123bfd40353dd2913d1,

title = "Superstable lipid vacuoles endow cartilage with its shape and biomechanics",

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.",

author = "Raul Ramos and Pham, {Kim T.} and Prince, {Richard C.} and Leiser-Miller, {Leith B.} and Prasad, {Maneeshi S.} and Xiaojie Wang and Nordberg, {Rachel C.} and Bielajew, {Benjamin J.} and Hu, {Jerry C.} and Kosuke Yamaga and Oh, {Ji Won} and Tao Peng and Rupsa Datta and Aksana Astrowskaja and Almet, {Axel A.} and Burns, {John T.} and Yuchen Liu and Guerrero-Juarez, {Christian Fernando} and Tran, {Bryant Q.} and Chu, {Yi Lin} and Nguyen, {Anh M.} and Hsi, {Tsai Ching} and Lim, {Norman T.L.} and Sandra Schoeniger and Ruiqi Liu and Pai, {Yun Ling} and Vadivel, {Chella K.} and Sandy Ingleby and McKechnie, {Andrew E.} and {van Breukelen}, Frank and Hoehn, {Kyle L.} and Rasweiler, {John J.} and Michinori Kohara and Loughry, {William J.} and Weldy, {Scott H.} and Raymond Cosper and Yang, {Chao Chun} and Lin, {Sung Jan} and Cooper, {Kimberly L.} and Santana, {Sharlene E.} and Bradley, {Jeffrey E.} and Kiebish, {Michael A.} and Michelle Digman and James, {David E.} and Merrill, {Amy E.} and Qing Nie and Schilling, {Thomas F.} and Astrowski, {Aliaksandr A.} and Potma, {Eric O.} and Garc{\'i}a-Castro, {Mart{\'i}n I.} and Athanasiou, {Kyriacos A.} and Behringer, {Richard R.} and Plikus, {Maksim V.}",

year = "2025",

month = jan,

day = "10",

doi = "10.1126/science.ads9960",

language = "English",

volume = "387",

pages = "eads9960",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6730",

}

Ramos, R, Pham, KT, Prince, RC, Leiser-Miller, LB, Prasad, MS, Wang, X, Nordberg, RC, Bielajew, BJ, Hu, JC, Yamaga, K, Oh, JW, Peng, T, Datta, R, Astrowskaja, A, Almet, AA, Burns, JT, Liu, Y, Guerrero-Juarez, CF, Tran, BQ, Chu, YL, Nguyen, AM, Hsi, TC, Lim, NTL, Schoeniger, S, Liu, R, Pai, YL, Vadivel, CK, Ingleby, S, McKechnie, AE, van Breukelen, F, Hoehn, KL, Rasweiler, JJ, Kohara, M, Loughry, WJ, Weldy, SH, Cosper, R, Yang, CC, Lin, SJ, Cooper, KL, Santana, SE, Bradley, JE, Kiebish, MA, Digman, M, James, DE, Merrill, AE, Nie, Q, Schilling, TF, Astrowski, AA, Potma, EO, García-Castro, MI, Athanasiou, KA, Behringer, RR & Plikus, MV 2025, 'Superstable lipid vacuoles endow cartilage with its shape and biomechanics', Science, 卷 387, 編號 6730, 頁 eads9960. https://doi.org/10.1126/science.ads9960

TY - JOUR

T1 - Superstable lipid vacuoles endow cartilage with its shape and biomechanics

AU - Ramos, Raul

AU - Pham, Kim T.

AU - Prince, Richard C.

AU - Leiser-Miller, Leith B.

AU - Prasad, Maneeshi S.

AU - Wang, Xiaojie

AU - Nordberg, Rachel C.

AU - Bielajew, Benjamin J.

AU - Hu, Jerry C.

AU - Yamaga, Kosuke

AU - Oh, Ji Won

AU - Peng, Tao

AU - Datta, Rupsa

AU - Astrowskaja, Aksana

AU - Almet, Axel A.

AU - Burns, John T.

AU - Liu, Yuchen

AU - Guerrero-Juarez, Christian Fernando

AU - Tran, Bryant Q.

AU - Chu, Yi Lin

AU - Nguyen, Anh M.

AU - Hsi, Tsai Ching

AU - Lim, Norman T.L.

AU - Schoeniger, Sandra

AU - Liu, Ruiqi

AU - Pai, Yun Ling

AU - Vadivel, Chella K.

AU - Ingleby, Sandy

AU - McKechnie, Andrew E.

AU - van Breukelen, Frank

AU - Hoehn, Kyle L.

AU - Rasweiler, John J.

AU - Kohara, Michinori

AU - Loughry, William J.

AU - Weldy, Scott H.

AU - Cosper, Raymond

AU - Yang, Chao Chun

AU - Lin, Sung Jan

AU - Cooper, Kimberly L.

AU - Santana, Sharlene E.

AU - Bradley, Jeffrey E.

AU - Kiebish, Michael A.

AU - Digman, Michelle

AU - James, David E.

AU - Merrill, Amy E.

AU - Nie, Qing

AU - Schilling, Thomas F.

AU - Astrowski, Aliaksandr A.

AU - Potma, Eric O.

AU - García-Castro, Martín I.

AU - Athanasiou, Kyriacos A.

AU - Behringer, Richard R.

AU - Plikus, Maksim V.

PY - 2025/1/10

Y1 - 2025/1/10

N2 - 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.

AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85214934891&partnerID=8YFLogxK

U2 - 10.1126/science.ads9960

DO - 10.1126/science.ads9960

M3 - Article

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