skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on January 10, 2026

Title: 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.  more » « less
Award ID(s):
1763272 2421118
PAR ID:
10581877
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more » ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; « less
Publisher / Repository:
Science
Date Published:
Journal Name:
Science
Volume:
387
Issue:
6730
ISSN:
0036-8075
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. null (Ed.)
    Purpose The larynx plays a role in swallowing, respiration, and voice production. All three functions change during ontogeny. We investigated ontogenetic shape changes using a mouse model to inform our understanding of how laryngeal form and function are integrated. We understand the characterization of developmental changes to larynx anatomy as a critical step toward using rodent models to study human vocal communication disorders. Method Contrast-enhanced micro-computed tomography image stacks were used to generate three-dimensional reconstructions of the CD-1 mouse ( Mus musculus ) laryngeal cartilaginous framework. Then, we quantified size and shape in four age groups: pups, weanlings, young, and old adults using a combination of landmark and linear morphometrics. We analyzed postnatal patterns of growth and shape in the laryngeal skeleton, as well as morphological integration among four laryngeal cartilages using geometric morphometric methods. Acoustic analysis of vocal patterns was employed to investigate morphological and functional integration. Results Four cartilages scaled with negative allometry on body mass. Additionally, thyroid, arytenoid, and epiglottic cartilages, but not the cricoid cartilage, showed shape change associated with developmental age. A test for modularity between the four cartilages suggests greater independence of thyroid cartilage shape, hinting at the importance of embryological origin during postnatal development. Finally, mean fundamental frequency, but not fundamental frequency range, varied predictably with size. Conclusion In a mouse model, the four main laryngeal cartilages do not develop uniformly throughout the first 12 months of life. High-dimensional shape analysis effectively quantified variation in shape across development and in relation to size, as well as clarifying patterns of covariation in shape among cartilages and possibly the ventral pouch. Supplemental Material https://doi.org/10.23641/asha.12735917 
    more » « less
  2. Starvation causes the accumulation of lipid droplets in the liver, a somewhat counterintuitive phenomenon that is nevertheless conserved from flies to humans. Much like fatty liver resulting from overfeeding, hepatic lipid accumulation (steatosis) during undernourishment can lead to lipotoxicity and atrophy of the liver. Here, we found that although surface populations ofAstyanax mexicanusundergo this evolutionarily conserved response to starvation, the starvation-resistant cavefish larvae of the same species do not display an accumulation of lipid droplets upon starvation. Moreover, cavefish are resistant to liver atrophy during starvation, providing a unique system to explore strategies for liver protection. Using comparative transcriptomics between zebrafish, surface fish, and cavefish, we identified the fatty acid transporter slc27a2a/fatp2 to be correlated with the development of fatty liver. Pharmacological inhibition of slc27a2a in zebrafish rescues steatosis and atrophy of the liver upon starvation. Furthermore, down-regulation of FATP2 in Drosophila larvae inhibits the development of starvation-induced steatosis, suggesting the evolutionarily conserved importance of the gene in regulating fatty liver upon nutrition deprivation. Overall, our study identifies a conserved, druggable target to protect the liver from atrophy during starvation. 
    more » « less
  3. Vertebrates have distinct tissues which are not present in invertebrate chordates nor other metazoans. The rise of these tissues also coincided with at least one round of whole-genome duplication as well as a suite of lineage-specific segmental duplications. Understanding whether novel genes lead to the origin and diversification of novel cell types, therefore, is of great importance in vertebrate evolution. Here we were particularly interested in the evolution of the vertebrate musculoskeletal system, the muscles and connective tissues that support a diversity of body plans. A major component of the musculoskeletal extracellular matrix (ECM) is fibrillar collagens, a gene family which has been greatly expanded upon in vertebrates. We thus asked whether the repertoire of fibrillar collagens in vertebrates reflects differences in the musculoskeletal system. To test this, we explored the diversity of fibrillar collagens in lamprey, a jawless vertebrate which diverged from jawed vertebrates (gnathostomes) more than five hundred million years ago and has undergone its own gene duplications. Some of the principal components of vertebrate hyaline cartilage are the fibrillar collagens type II and XI, but their presence in cartilage development across all vertebrate taxa has been disputed. We particularly emphasized the characterization of genes in the lamprey hyaline cartilage, testing if its collagen repertoire was similar to that in gnathostomes. Overall, we discovered thirteen fibrillar collagens from all known gene subfamilies in lamprey and were able to identify several lineage-specific duplications. We found that, while the collagen loci have undergone rearrangement, the Clade A genes have remained linked with the hox clusters, a phenomenon also seen in gnathostomes. While the lamprey muscular tissue was largely similar to that seen in gnathostomes, we saw considerable differences in the larval lamprey skeletal tissue, with distinct collagen combinations pertaining to different cartilage types. Our gene expression analyses were unable to identify type II collagen in the sea lamprey hyaline cartilage nor any other fibrillar collagen during chondrogenesis at the stages observed, meaning that sea lamprey likely no longer require these genes during early cartilage development. Our findings suggest that fibrillar collagens were multifunctional across the musculoskeletal system in the last common ancestor of vertebrates and have been largely conserved, but these genes alone cannot explain the origin of novel cell types. 
    more » « less
  4. The size and shape of articular cartilage in the limbs of extant vertebrates are highly variable, yet they are critical for understanding joint and limb function in an evolutionary context. For example, inferences about unpreserved articular cartilage in early tetrapods have implications for how limb length, joint range of motion, and muscle leverage changed over the tetrapod water-land transition. Extant salamanders, which are often used as functional models for early limbed vertebrates, have much thicker articular cartilage than most vertebrate groups, but the exact proportion of cartilage and how it varies across salamander species is unknown. I aimed to quantify this variation in a sample of 13 salamanders representing a broad range of sizes, modes of life, and genera. Using contrast-enhanced micro-CT, cartilage dimensions and bone length were measured non-destructively in the humerus, radius, ulna, femur, tibia, and fibula of each specimen. Cartilage correction factors were calculated as the combined thickness of the proximal and distal cartilages divided by the length of the bony shaft. Articular cartilage added about 30% to the length of the long bones on average. Cartilage was significantly thicker in aquatic salamanders (42 ± 14% in the humerus and 35 ± 8 in the femur) than in terrestrial salamanders (21 ± 7% in both humerus and femur). There was no consistent relationship between relative cartilage thickness and body size or phylogenetic relatedness. In addition to contributing to limb length, cartilage caps increased the width and breadth of the epiphyses by amounts that varied widely across taxa. To predict the effect of salamander-like cartilage correction factors on muscle leverage, a simplified model of the hindlimb of the Devonian stem tetrapod Acanthostega was built. In this model, the lever arms of muscles that cross the hip at an oblique angle to the femur was increased by up to six centimeters. Future reconstructions of osteological range of motion and muscle leverage in stem tetrapods and stem amphibians can be made more rigorous by explicitly considering the possible effects of unpreserved cartilage and justifying assumptions based on available data from extant taxa, including aquatic and terrestrial salamanders. 
    more » « less
  5. Abstract Articular cartilage is a thin layer of a solid matrix swollen by fluid, and it protects joints from damage via poroviscoelastic damping. Our previous experimental and simulation studies showed that cartilage-like poroviscoelastic damping could widen the range of damping methods in a low-frequency range (<100 Hz). Thus, the current study aimed to realize cartilage-like damping capacity by single- and two-indenter–foam poroviscoelastic dampers in a low-frequency range. Multiple single-indenter–foam dampers were designed by combining foam sheets with different pore diameters and indenters with different radii. Their damping capacity was investigated by dynamic mechanical analysis in a frequency range of 0.5–100 Hz. Single-indenter–foam dampers delivered peak damping frequencies that depended on the foam’s pore diameter and characteristic diffusion length (contact radii). Those dampers maximize the damping capacity at the desired frequency (narrowband performance). A mechanical model combined with simple scaling laws was shown to relate poroelasticity to the peak damping frequencies reasonably well. Finally, combinations of single-indenter–foam dampers were optimized to obtain a two-indenter–foam damper that delivered nearly rate-independent damping capacity within 0.5–100 Hz (broadband performance). These findings suggested that cartilage-like poroviscoelastic dampers can be an effective mean of passive damping for narrowband and broadband applications. 
    more » « less