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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Superstable lipid vacuoles endow cartilage with its shape and biomechanics.
Science
January 2025
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
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.
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Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, PR China; College of Pharmaceutical Sciences, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, PR China. Electronic address:
Transarterial chemoembolization (TACE) with free doxorubicin-lipiodol emulsions (free DOX/L) is a favored clinical treatment for advanced hepatocellular carcinoma (HCC) patients ineligible for radical therapies; however, its inferior colloidal stability not only greatly reduces its tumor retention but also hastens drug release into blood circulation, leading to suboptimal clinical outcomes. Here, we find that disulfide-crosslinked polymersomes carrying doxorubicin (Ps-DOX) form super-stable and homogenous water-in-oil microemulsions with lipiodol (Ps-DOX/L). Ps-DOX/L microemulsions had tunable sizes ranging from 14 to 44 μm depending on the amount of Ps-DOX, were stable over 2 months storage as well as centrifugation, and exhibited nearly zero-order DOX release within 15 days.
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State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
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