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Updated: Feb 2, 2026

Establishment of a Surgically-induced Model in Mice to Investigate the Protective Role of Progranulin in Osteoarthritis
Published on: February 25, 2014
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.
Objective:
CD14 is a monocyte/macrophage pattern-recognition receptor that modulates innate inflammatory signaling. Soluble CD14 levels in knee OA synovial fluids are associated with symptoms and progression of disease. Here we investigate the role of this receptor in development of OA using a murine joint injury model of disease.
Methods:
10-week-old Male C57BL/6 (WT) and CD14-deficient (CD14-/-) mice underwent destabilization of the medial meniscus (DMM) surgery to induce OA. Joint histopathology was used to examine cartilage damage, and microCT to evaluate subchondral bone (SCB) remodeling at 6 and 19 weeks after surgery. Synovial and fat pad expression of macrophage markers (F4/80, CD11c, CD68, iNOS, CCR7, CD163 and CD206) was assessed by flow cytometry and droplet digital (dd)PCR. Changes in locomotive activity indicative of joint pain were evaluated longitudinally up to 16 weeks by automated behavioral analysis.
Results:
Early cartilage damage scores 6 weeks post-DMM were similar in both strains (Mean score ±SEM WT: 4.667±1.38, CD14-/-: 4.6±0.6), but at 19 weeks were less severe in CD14-/- (6.0±0.46) than in WT mice (13.44±2.5, p = 0.0002). CD14-/- mice were protected from both age-related and post-surgical changes in SCB mineral density and trabecular thickness. In addition, CD14-/- mice were protected from decreases in climbing activity (p = 0.015 vs. WT, 8 weeks) observed after DMM. Changes in synovial/fat pad expression of CCR7, a marker of M1 macrophages, were slightly reduced post-DMM in the absence of CD14, while expression of CD68 (pan-macrophage marker) and CD163 (M2 marker) were unchanged.
Conclusion:
CD14 plays an important role in progression of structural and functional features of OA in the DMM model, and may provide a new target for therapeutic development.
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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