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Anabolic indices of matrix proteins identify regenerative small RNA intrinsic to human cartilage

Hsueh, Ming Feng ; Önnerfjord, Patrik LU orcid and Kraus, Virginia B. (2025) In Science Advances 11(28).
Abstract

Some vertebrates regenerate appendages through the action of small noncoding RNAs (smRNAs) expressed in their blastema. Inspired by these models, we investigated whether similar smRNA-mediated mechanisms might contribute to the intrinsic repair capacity of human cartilage. Although humans lack the capacity to regenerate entire limbs, digit tip regrowth and joint cartilage repair following joint distraction suggest latent regenerative potential. Using mass spectrometry and RNA sequencing, we quantified anabolic indices of cartilage extracellular matrix proteins and identified 69 smRNAs correlated with cartilage regeneration in osteoarthritis—six concordantly regulated across species (human, axolotl, zebrafish, and bichir)—including... (More)

Some vertebrates regenerate appendages through the action of small noncoding RNAs (smRNAs) expressed in their blastema. Inspired by these models, we investigated whether similar smRNA-mediated mechanisms might contribute to the intrinsic repair capacity of human cartilage. Although humans lack the capacity to regenerate entire limbs, digit tip regrowth and joint cartilage repair following joint distraction suggest latent regenerative potential. Using mass spectrometry and RNA sequencing, we quantified anabolic indices of cartilage extracellular matrix proteins and identified 69 smRNAs correlated with cartilage regeneration in osteoarthritis—six concordantly regulated across species (human, axolotl, zebrafish, and bichir)—including microRNA 21 (miR-21). miR-21 enhanced the expression of key cartilage formation genes, reduced cartilage degradation, and suppressed cytokine secretion from human cartilage and chondrocytes. In contrast to the knee and hip, ankle cartilage exhibited regenerative capacity under osteoarthritic stress, offering a model for a regeneration-permissive joint environment that could inform osteoarthritis therapies.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Advances
volume
11
issue
28
article number
eadu8440
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:40644557
  • scopus:105011136729
ISSN
2375-2548
DOI
10.1126/sciadv.adu8440
language
English
LU publication?
yes
additional info
Publisher Copyright: Copyright © 2025 The Authors, some rights reserved.
id
ed5368b7-736d-49aa-9c41-aaebc41f4f27
date added to LUP
2025-12-09 14:53:32
date last changed
2025-12-09 14:53:53
@article{ed5368b7-736d-49aa-9c41-aaebc41f4f27,
  abstract     = {{<p>Some vertebrates regenerate appendages through the action of small noncoding RNAs (smRNAs) expressed in their blastema. Inspired by these models, we investigated whether similar smRNA-mediated mechanisms might contribute to the intrinsic repair capacity of human cartilage. Although humans lack the capacity to regenerate entire limbs, digit tip regrowth and joint cartilage repair following joint distraction suggest latent regenerative potential. Using mass spectrometry and RNA sequencing, we quantified anabolic indices of cartilage extracellular matrix proteins and identified 69 smRNAs correlated with cartilage regeneration in osteoarthritis—six concordantly regulated across species (human, axolotl, zebrafish, and bichir)—including microRNA 21 (miR-21). miR-21 enhanced the expression of key cartilage formation genes, reduced cartilage degradation, and suppressed cytokine secretion from human cartilage and chondrocytes. In contrast to the knee and hip, ankle cartilage exhibited regenerative capacity under osteoarthritic stress, offering a model for a regeneration-permissive joint environment that could inform osteoarthritis therapies.</p>}},
  author       = {{Hsueh, Ming Feng and Önnerfjord, Patrik and Kraus, Virginia B.}},
  issn         = {{2375-2548}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{28}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{Anabolic indices of matrix proteins identify regenerative small RNA intrinsic to human cartilage}},
  url          = {{http://dx.doi.org/10.1126/sciadv.adu8440}},
  doi          = {{10.1126/sciadv.adu8440}},
  volume       = {{11}},
  year         = {{2025}},
}