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

Autor: Carla R. Scanzello, Kurt D. Hankenson, George R. Dodge, Cheng Zhou, V. Nguyen, Ryan Smalley, Nisha Sambamurthy
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Physiology
Lipopolysaccharide Receptors
Gene Expression
Disease
Osteoarthritis
Menisci
Tibial
White Blood Cells
Mice
0302 clinical medicine
Skeletal Joints
Animal Cells
Medicine and Health Sciences
Macrophage
Receptor
Musculoskeletal System
Mammals
Multidisciplinary
Pattern recognition receptor
Eukaryota
Climbing
3. Good health
medicine.anatomical_structure
Connective Tissue
Receptors
Pattern Recognition
Vertebrates
Medicine
Cellular Types
Anatomy
Research Article
CD14
Immune Cells
Inflammatory Diseases
Science
Immunology
Rodents
03 medical and health sciences
Rheumatology
medicine
Genetics
Animals
RNA
Messenger
030203 arthritis & rheumatology
Blood Cells
business.industry
Biological Locomotion
Cartilage
Monocyte
Macrophages
Arthritis
Organisms
Biology and Life Sciences
X-Ray Microtomography
Cell Biology
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Biological Tissue
Gene Expression Regulation
Amniotes
Joints
business
Zdroj: PLoS ONE, Vol 13, Iss 11, p e0206217 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: ObjectiveCD14 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.Methods10-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.ResultsEarly 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.ConclusionCD14 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.
Databáze: OpenAIRE
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