Modulation of Gene Expression in Infrapatellar Fat Pad–Derived Mesenchymal Stem Cells in Osteoarthritis

Abstract

Aim In the osteoarthritis (OA) disease, all structures of the joint are involved. The infrapatellar Hoffa fat pad is rich in macrophages and granulocytes, which also represents a source of adipose mesenchymal progenitor cells (ASC) cells. In our study, we analyze how OA affects the ability of ASC-derived from Hoffa's fat pad to differentiate into chondrocytes. Material and methodology We took knee Hoffa's pad samples and adipose tissue from the proximal thigh from 6 patients diagnosed with severe OA and from another 6 patients with an anterior cruciate ligament (ACL) rupture without OA. From all the patients, we took subcutaneous adipose tissue from the thigh, as the control group. Samples of synovial fluid (SF) were also extracted. The gene expression was analyzed by real-time quantitative polymerase chain reaction. Results PTH1R and MMP13 expression during chondrogenic differentiation were similar between OA and ACL groups, while the expression of OPG, FGF2, TGFβ, MMP3 were significantly lower in the OA group. Exposure of differentiated ASC to OA SF induced an increase in the expression of OPG, PTH1R, and MMP13 and a decrease in the expression of FGF2 in cell culture of the ACL group. However, expression of none of these factors was altered by the OA synovial fluid in ASC cells of the OA group. Conclusion OA of the knee also affects the mesenchymal stem cells of Hoffa fat, suggesting that Hoffa fat is a new actor in the OA degenerative process that can contribute to the origin, onset, and progression of the disease.

In vitro and in vivo potentialities for cartilage repair from human advanced knee osteoarthritis synovial fluid-derived mesenchymal stem cells

“…Since the sixties, it has long be known that SF from arthritic patients of various conditions, including OA, contains cells capable of in vitro proliferation, but their phenotypic characterization and multipotentiality were demonstrated in 2004 [ 25 ]. Their origin has been debated: blood irrigation, shedding from synovium [ 26 ], especially type B synovial lining, disrupted superficial cartilage layer [ 27 ], subchondral bone, infra-patellar pad [ 28 ]. For a decade, the presence of SF-MSCs in normal SF, increasing in early human OA, has been demonstrated [ 8 ].…”

“…One possible explanation of this peculiar chondrogenic commitment may be the physio-pathological microenvironment of the SF-MSCs used herein; all harvested in end-stage OA knees undergoing total knee joint replacement. In degenerative conditions, there is mainly a catabolic environment with a significant increase of TNFα and a significant decrease of TGF-ß1 [ 28 ]. During OA, synovitis causes hypoxia [ 47 ], hypercapnia, and acidity in synovial fluid [ 48 ].…”

Recent Advance in Source, Property, Differentiation, and Applications of Infrapatellar Fat Pad Adipose-Derived Stem Cells

“…The osteogenic differentiation potential of IPFP-ASCs is stronger in rheumatoid arthritis than in osteoarthritis, which may be related to tissue necrosis factor-α (TNF-α) [31]. Osteoarthritis can affect the chondrogenic differentiation potential of IPFP-ASCs [32]. The decreased chondrogenic differentiation potential of IPFP-ASCs may be associated with the downregulation of TGF-β gene expression in osteoarthritis [33].…”

“…In addition, there are studies on IPFP-ASC differentiation at gene level. Bravo et al [32] have found that during IPFP-ASC chondrogenic differentiation, the expressions of PTFR and MMP13 are similar between the patients with knee osteoarthritis and the individuals with healthy knees, but the expressions of OPG, FGF2, TGF, and MMP3 are significantly lower in the patients with knee osteoarthritis than in the individuals with healthy knees.…”

Magnetic Resonance Imaging of Hoffa’s Fat Pad

“…жировое тело склонно к изменению своей конфигурации при движениях в коленном суставе, тем самым обеспечивая механическую амортизацию и облегчая распределение синовиальной жидкости [10,11]. Диагностика изменений объема и структуры жировой клетчатки важна ввиду взаимосвязи её патологии с болевым синдромом в переднем отделе коленного сустава, а также возможной взаи-мосвязи с ранним формированием остеоартроза [12,13].…”