Early removal of the infrapatellar fat pad/synovium complex beneficially alters the pathogenesis of moderate stage idiopathic knee osteoarthritis in male Dunkin Hartley guinea pigs

Arthritis Research & Therapy

Research

Tammy L. Haut Donahue¹  Ryan Ek²  Nicole Vigon²  Gerardo E. Narez²  Katie J. Sikes³  Angela J. Marolf⁴  Madeline M. Sykes⁵  Kayley M. Patton⁵  Joseph L. Sanford⁵  Margaret A. Campbell⁵  Lauren B. Radakovich⁵  Kelly S. Santangelo⁵  Maryam F. Afzali⁵ 

[1] Biomedical Engineering Department, The University of Memphis, 3806 Norriswood, 38152, Memphis, TN, USA;Department of Biomedical Engineering, S631 Life Sciences Laboratory, University of Massachusetts, Amherst, 240 Thatcher Road, 01003, Amherst, MA, USA;Department of Clinical Sciences, Colorado State University, 1678 Clinical Sciences, 80523, Fort Collins, CO, USA;Department of Environmental and Radiological Health Sciences, Colorado State University, 123 Flint Cancer Center, 80523, Fort Collins, CO, USA;Department of Microbiology, Immunology and Pathology, Colorado State University, 200 West Lake Street, 80523, Fort Collins, CO, USA;

关键词: Osteoarthritis;    Infrapatellar fat pad/synovium complex;    Gait;    Inflammation;    Biomechanics;    Trace elements;    Hartley guinea pig;   

DOI  :  10.1186/s13075-022-02971-y

 received in 2022-09-16, accepted in 2022-12-02,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe infrapatellar fat pad (IFP) is the largest adipose deposit in the knee; however, its contributions to the homeostasis of this organ remain undefined. To determine the influence of the IFP and its associated synovium (IFP/synovium complex or IFP/SC) on joint health, this study evaluated the progression of osteoarthritis (OA) following excision of this unit in a rodent model of naturally-occurring disease.MethodsMale Dunkin-Hartley guinea pigs (n=18) received surgical removal of the IFP in one knee at 3 months of age; contralateral knees received sham surgery as matched internal controls. Mobility and gait assessments were performed prior to IFP/SC removal and monthly thereafter. Animals were harvested at 7 months of age. Ten set of these knees were processed for microcomputed tomography (microCT), histopathology, transcript expression analyses, and immunohistochemistry (IHC); 8 sets of knees were dedicated to microCT and biomechanical testing (material properties of knee joints tissues and anterior drawer laxity).ResultsFibrous connective tissue (FCT) developed in place of the native adipose depot. Gait demonstrated no significant differences between IFP/SC removal and contralateral hindlimbs. MicroCT OA scores were improved in knees containing the FCT. Quantitatively, IFP/SC-containing knees had more osteophyte development and increased trabecular volume bone mineral density (vBMD) in femora and tibiae. Histopathology confirmed maintenance of articular cartilage structure, proteoglycan content, and chondrocyte cellularity in FCT-containing knees. Transcript analyses revealed decreased expression of adipose-related molecules and select inflammatory mediators in FCTs compared to IFP/SCs. This was verified via IHC for two key inflammatory agents. The medial articular cartilage in knees with native IFP/SCs showed an increase in equilibrium modulus, which correlated with increased amounts of magnesium and phosphorus.Discussion/conclusionFormation of the FCT resulted in reduced OA-associated changes in both bone and cartilage. This benefit may be associated with: a decrease in inflammatory mediators at transcript and protein levels; and/or improved biomechanical properties. Thus, the IFP/SC may play a role in the pathogenesis of knee OA in this strain, with removal prior to disease onset appearing to have short-term benefits.

【 授权许可】

CC BY   
© The Author(s) 2022

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