Gene expression, protein profiling, and chemotactic activity of infrapatellar fat pad mesenchymal stem cells in pathologies of the knee joint

J Cell Physiol. 2019 Aug;234(10):18917-18927. doi: 10.1002/jcp.28532. Epub 2019 Mar 25.

Abstract

The infrapatellar fat pad (IPFP) is a periarticular adipose knee tissue. This tissue contains a large number of mesenchymal stem cells (MSCs). In the present work, we wanted to study the IPFP MSCs and their relationship and differences in two groups, anterior cruciate ligament (ACL) ruptures knees and ostheoarthrosis (OA). The IPFP of 42 patients with OA or ACL rupture were analyzed. Isolation, primary culture, and a genetic and proteomic study of MSCs from IPFP were performed. Gene expression of IL-6, tumor necrosis factor (TNF), IL-8, HSPA1A (Hsp70), CXCL10, RANTES, MMP1, MMP3, TIMP1, and BMP7 was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). We analyzed MSCs from from 12 diferents patients in two cellular pools (6 from AO disease and 6 from ALC rupture to form two cell pool), for the iTRAQ Proteomic Assay. The conditional media were used in quantitative analysis of MSC soluble factors by Luminex and for de migration assay. A higher gene expression of IL-6, TNF, CXCL10, RANTES, and MMP1 and OPG in MSCs from OA versus ACL (p < 0.05) was observed. Conversely HSPA1A, TIMP1, and RANKL showed a significant lower expression in OA-MSCs (p < 0.05). In the secretome analysis, adipsin and visfantin levels in the supernatants from OA-MSCs were lower (p < 0.05) respect to ACL-MSCs. Also, the monocytic cells migrated two-folds in the presence of conditioned media from OA-MSCs patients versus patients with ACL-MSC. The infrapatellar pad should be considered as an adipose tissue capable of producing and excreting inflammatory mediators directly in the knee joint, influencing the development and progression of knee joint pathologies.

Keywords: ACL; OA; infrapatellar fat pad; mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism*
  • Adult
  • Anterior Cruciate Ligament / cytology
  • Anterior Cruciate Ligament / pathology
  • Anterior Cruciate Ligament Injuries / pathology*
  • Cell Movement / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology
  • Cytokines / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Knee Joint / cytology*
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Middle Aged
  • Osteoarthritis / pathology*
  • Patella / cytology*
  • Transcriptome
  • Young Adult

Substances

  • Culture Media, Conditioned
  • Cytokines