Systemic neutralization of TGF-β attenuates osteoarthritis

Liang Xie, Francis Tintani, Xiao Wang, Fengfeng Li, Gehua Zhen, Tao Qiu, Mei Wan, Janet Crane, Qianming Chen, Xu Cao

Research output: Contribution to journalArticle

Abstract

Osteoarthritis (OA) is a major source of pain and disability worldwide with no effective medical therapy due to poor understanding of its pathogenesis. Transforming growth factor β (TGF-β) has been reported to play a role in subchondral bone pathology and articular cartilage degeneration during the progression of OA. In this study, we demonstrated that systemic use of a TGF-β–neutralizing antibody (1D11) attenuates OA progression by targeting subchondral bone pathological features in rodent OA models. Systemic administration of 1D11 preserves the subchondral bone microarchitecture, preventing articular cartilage degeneration by inhibition of excessive TGF-β activity, in both subchondral bone and the circulation. Moreover, the aberrant increases in the numbers of blood vessels, nestin+ mesenchymal stromal/stem cells, and osterix+ osteoblast progenitors were normalized by 1D11 systemic injection. Thus, systemic neutralization of excessive TGF-β ligands effectively prevented OA progression in animal models, with promising clinical implications for OA treatment.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume1376
Issue number1
DOIs
StatePublished - Jan 1 2016

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Keywords

  • TGF-β
  • antibody
  • cartilage
  • osteoarthritis
  • subchondral bone

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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