Regional Differences Between Perisynovial and Infrapatellar Adipose Tissue Depots and Their Response to Class II and Class III Obesity in Patients With Osteoarthritis

Arthritis Rheumatol. 2017 Jul;69(7):1396-1406. doi: 10.1002/art.40102. Epub 2017 Jun 10.


Objective: Obesity is associated with an increased risk of developing osteoarthritis (OA), which is postulated to be secondary to adipose tissue-dependent inflammation. Periarticular adipose tissue depots are present in synovial joints, but the association of this tissue with OA has not been extensively explored. The aim of this study was to investigate differences in local adipose tissue depots in knees with OA and characterize the changes related to class II and class III obesity in patients with end-stage knee OA.

Methods: Synovium and the infrapatellar fat pad (IPFP) were collected during total knee replacement from 69 patients with end-stage OA. Histologic changes, changes in gene and protein expression of adiponectin, peroxisome proliferator-activated receptor γ (PPARγ), and Toll-like receptor 4 (TLR-4), and immune cell infiltration into the adipose tissue were investigated.

Results: IPFP and synovium adipose tissue depots differed significantly and were influenced by the patient's body mass index. Compared to adipocytes from the IPFP and synovium of lean patients, adipocytes from the IPFP of obese patients were significantly larger and the synovium of obese patients displayed marked fibrosis, increased macrophage infiltration, and higher levels of TLR4 gene expression. The adipose-related markers PPARγ in the IPFP and adiponectin and PPARγ in the synovium were expressed at lower levels in obese patients compared to lean patients. Furthermore, there were increased numbers of CD45+ hematopoietic cells, CD45+CD14+ total macrophages, and CD14+CD206+ M2-type macrophages in both the IPFP and synovial tissue of obese patients.

Conclusion: These differences suggest that IPFP and synovium may contain 2 different white adipose tissue depots and support the theory of inflammation-induced OA in patients with class II or III obesity. These findings warrant further investigation as a potentially reversible, or at least suppressible, cause of OA in obese patients.

MeSH terms

  • Adipocytes / metabolism
  • Adiponectin / genetics
  • Adiponectin / metabolism
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology*
  • Arthroplasty, Replacement, Knee
  • Blotting, Western
  • Body Mass Index
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Knee Joint / metabolism
  • Knee Joint / pathology*
  • Macrophages
  • Obesity / complications
  • Obesity, Morbid / complications*
  • Osteoarthritis, Knee / complications
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / pathology*
  • Osteoarthritis, Knee / surgery
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Patella
  • Real-Time Polymerase Chain Reaction
  • Synovial Membrane
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism


  • ADIPOQ protein, human
  • Adiponectin
  • PPAR gamma
  • TLR4 protein, human
  • Toll-Like Receptor 4