The Unexplored Role of Intra-articular Adipose Tissue in the Homeostasis and Pathology of Articular Joints

Abstract

Intra-articular adipose tissue deposits known as articular fat pads (AFPs) are described to exist within synovial joints. Their assumed role in normal joint biomechanics is increasingly objectivized by means of advanced methods of functional imaging. AFPs possess structural similarity with body subcutaneous white adipose tissue (WAT), however, seems to be regulated by independent metabolic loops. AFP dimension are conserved during extreme WAT states: obesity, metabolic syndrome, lipodystrophy, and cachexia. Hoffa fat pad (HFP) in the knee is increasingly recognized as a major player in pathological joint states such as anterior knee pain and osteoarthritis. HFP contains numerous population of mesenchymal and endothelial progenitors; however, the possible role of mature adipocytes in the maintenance of stem cell niche is unknown. We propose that AFP is an active component of the joint organ with multifunctional roles in the maintenance of joint homeostasis. Endowed with a rich network of sensitive nervous fibbers, AFPs may act as a proprioceptive organ. Adipokines and growth factors released by AFP-resident mature adipocytes could participate in the maintenance of progenitor stem cell niche as well as in local immune regulation. AFP metabolism may be locally controlled, correlated with but independent of WAT homeostasis. The identification of AFP role in normal joint turnover and its possible implication in pathological states could deliver diagnostic and therapeutic targets. Drug and/or cell therapies that restore AFP structure and function could become the next step in the design of disease modifying therapies for disabling joint conditions such as osteoarthritis and inflammatory arthritis.

Computational deconvolution of synovial tissue cellular composition: presence of adipocytes in synovial tissue decreased during arthritis pathogenesis and progression

“…The biomechanical and homeostatic role of synovial fat tissue and synovial adipocytes remains incompletely understood (8). At the molecular level, adipocytes in synovial tissue may play multiple critical roles in maintaining healthy joints, including energy metabolism and maintaining the stem cell niche (25). Adipocytes secrete both proinflammatory (such as TNF, IL6, IL8) and anti-inflammatory adipokines and cyto-kines (11,24,33).…”

Assessment and Comparison of the Efficacy of Methotrexate, Prednisolone, Adalimumab, and Tocilizumab on Multipotency of Mesenchymal Stem Cells

“…In addition to the influences of antirheumatic drugs on dominant potential factors for articular regenerative, the effects of these drugs on adipogenic induction is of interest. Although it has been hypothesized that synovial adipocytes may contribute to maintenance of articular energy metabolism and the stem cell niche, the precise role of adipocytes in the regulation of cartilage homeostasis remains poorly understood (Labusca and Zugun-Eloae, 2018). Direct application of methotrexate downregulated the expression of FABP4 in a dose-dependent manner, whereas prednisolone only slightly inhibited FABP4 induction.…”

The Lateral Knee Radiograph: A Detailed Review

“…It has been suggested that in addition to reducing mechanical forces, the Hoffa fat pad, as well as other fat pad within the body, serves a proprioceptive role. 2…”