Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance

Z. Liu, Y. Ren, A. J. Mirando, C. Wang, M. J. Zuscik, R. J. O'Keefe, M. J. Hilton

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objective: Notch signaling has been identified as a critical regulator in cartilage development and joint maintenance, and loss of Notch signaling in all joint tissues results in an early and progressive osteoarthritis (OA)-like pathology. This study investigated the targeted cell population within the knee joint in which Notch signaling is required for normal cartilage and joint integrity. Methods: Two loss-of-function mouse models were generated with tissue-specific knockout of the core Notch signaling component, RBPjκ. The AcanCreERT2 transgene specifically removed Rbpjκ floxed alleles in postnatal joint chondrocytes, while the Col1Cre(2.3kb) transgene deleted Rbpjκ in osteoblast populations, including subchondral osteoblasts. Mutant and control mice were analyzed via histology, immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (qPCR), X-ray, and microCT imaging at multiple time-points. Results: Loss of Notch signaling in postnatal joint chondrocytes results in a progressive OA-like pathology, and triggered the recruitment of non-targeted fibrotic cells into the articular cartilage potentially due to mis-regulated chemokine expression from within the cartilage. Upon recruitment, these fibrotic cells produced degenerative enzymes that may lead to the observed cartilage degradation and contribute to a significant portion of the age-related OA-like pathology. On the contrary, loss of Notch signaling in subchondral osteoblasts did not affect normal cartilage development or joint maintenance. Conclusions: RBPjκ-dependent Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance.

Original languageEnglish (US)
Pages (from-to)740-751
Number of pages12
JournalOsteoarthritis and Cartilage
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Fingerprint

Osteoblasts
Cartilage
Articular Cartilage
Chondrocytes
Joints
Maintenance
Pathology
Osteoarthritis
Transgenes
Tissue
Histology
Polymerase chain reaction
X-Ray Microtomography
Knee Joint
Chemokines
Population
Enzymes
Real-Time Polymerase Chain Reaction
Cells
Immunohistochemistry

Keywords

  • Cartilage
  • Chondrocytes
  • Notch signaling
  • Osteoarthritis
  • Subchondral bone
  • Synovium

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

Cite this

Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance. / Liu, Z.; Ren, Y.; Mirando, A. J.; Wang, C.; Zuscik, M. J.; O'Keefe, R. J.; Hilton, M. J.

In: Osteoarthritis and Cartilage, Vol. 24, No. 4, 01.04.2016, p. 740-751.

Research output: Contribution to journalArticle

Liu, Z. ; Ren, Y. ; Mirando, A. J. ; Wang, C. ; Zuscik, M. J. ; O'Keefe, R. J. ; Hilton, M. J. / Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance. In: Osteoarthritis and Cartilage. 2016 ; Vol. 24, No. 4. pp. 740-751.
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