Deficiency of the pattern-recognition receptor CD14 protects against joint pathology and functional decline in a

Nisha Sambamurthy1,2, Cheng Zhou1,2, Vu Nguyen1,2

  • 1Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.

Plos One
|November 29, 2018
PubMed
Abstract

Insights

CD14 deficiency protected mice from osteoarthritis progression and joint pain in a murine model. This suggests CD14 is a potential therapeutic target for treating osteoarthritis.

Area of Science:

  • Immunology
  • Rheumatology
  • Orthopedics

Background:

  • CD14 is a pattern-recognition receptor on monocytes/macrophages involved in innate inflammatory signaling.
  • Elevated soluble CD14 in synovial fluid correlates with osteoarthritis (OA) symptoms and disease progression.

Purpose of the Study:

  • To investigate the role of the CD14 receptor in the development and progression of osteoarthritis (OA).
  • To evaluate the therapeutic potential of targeting CD14 in OA using a murine model.

Main Methods:

  • Destabilization of the medial meniscus (DMM) surgery was performed on wild-type (WT) and CD14-deficient (CD14-/-) mice to induce OA.
  • Histopathology and microCT were used to assess cartilage damage and subchondral bone remodeling.
  • Macrophage markers were analyzed via flow cytometry and ddPCR; locomotive activity was monitored to evaluate joint pain.

Main Results:

  • CD14-/- mice showed significantly less cartilage damage at 19 weeks post-DMM compared to WT mice.
  • CD14 deficiency protected against subchondral bone changes and preserved locomotive activity after DMM.
  • Absence of CD14 led to reduced expression of CCR7 (M1 macrophage marker) but did not alter CD68 or CD163 expression.

Conclusions:

  • CD14 plays a significant role in the progression of structural and functional aspects of osteoarthritis.
  • Targeting CD14 may offer a novel therapeutic strategy for managing osteoarthritis.

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