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. 2023 Feb 15;19(5):1185–1213. doi: 10.1007/s12015-023-10517-1

Table 2.

Function of major conditioned medium components in the context of the biology of chondrocytes

Component Function Ref Proved presence
Proteins
  MMP-2

- degradation and remodelling of ECM;

- involvement in inflammatory processes;

- promotion of cell attachment;

- promotion of proliferation and differentiation;

- promotion of programmed cell death;

- regulation of the destruction of cartilage by TGF-β activity;

- recruitment of osteoblasts involved in tissue remodelling

 [66–69] [21, 43, 70, 71]
  MMP-9

- degradation of ECM;

- involvement in inflammatory processes;

- recruitment of osteoclasts into hypertrophic zones;

- formation of endochondral bone

 [66, 68, 69] [21, 43, 70]
  MMP-13

- cleaving of collagen types I, II, III;

- degradation of cellular matrix and non-cellular components

 [72] [30]
  MMP-19 - degradation of aggrecan, COMP proteins, type IV collagen, type I gelatine, laminin, fibronectin and nidogen [73, 74] [75]
  TIMP-1

- inhibition of fibrotic activity;

- prevention of cartilage degradation;

- inhibition of MMPs activity;

- suppression of pain

 [43, 71, 76–78] [43, 70, 71, 76]
  TIMP-2 [43, 70]
  VIM

- promotion of chondrogenic differentiation of MPC;

- regulation of the synthesis of the ECM;

- enhancement of the expression of the cartilage markers;

- maintenance of the chondrocytes phenotype

 [79, 80] [71, 81]
  SERPINE1

- prevention of cartilage degradation;

- tissue remodelling;

- fibre formation;

- inhibition of plasmin and cellular matrix metalloproteinases

 [82] [76, 81]
  SERPINE2

- prevention of cartilage breakdown;

- inhibition of MMP-13 expression

 [83] [81]
Cytokines, growth factors and chemokines
  TGF-β

- tissue development;

- chondrocyte differentiation from early to final stages;

- proliferation and differentiation;

- maintenance of the chondrocytes;

- inhibition of hypertrophy;

- reduction of oxidative stress

 [84, 85] [30, 44, 64, 75, 86–88]
  CCL2 - inflammatory response [89] [21, 76, 86, 90, 91]
  VEGF

- proliferation and migration of endothelial progenitor cells;

- chondrocyte survival;

- endochondral ossification;

- angiogenesis;

- inflammatory process;

- pain receptor sensitisation

 [92–95] [40, 44, 75, 86–88, 96]
  HGF-1

- cell survival and proliferation;

- cellular matrix metabolism;

- inflammatory response;

- osteochondral turnover;

- bone remodelling;

- regeneration of osteoarticular tissues

 [97] [21, 40, 44, 86, 87, 96]
  LIF

- proteoglycans resorption in cartilage;

- inflammatory and catabolic processes;

- cell differentiation;

- acute phase protein synthesis;

- stimulation of calcium ion release in bone;

- immune response;

- cartilage degradation in arthritis

 [98–101] [81, 86]
  FGF-2

- inhibition of aggrecan degradation;

- TIMP-1 synthesis;

- MMP-1 and MMP-3 synthesis;

- cartilage protection;

- inhibition of cartilage components degradation

 [102, 103] [40, 44, 96]
  PDGF

- chemotaxis;

- angiogenesis;

- cell mitosis;

- inhibition of inflammatory processes;

- anti-apoptotic;

- increase in the level of type II collagen;

- reduction in the level of collagen X

 [104, 105] [21, 44, 64, 75, 87]
  IFN-γ

- communication between immune cells;

- activation of defence mechanisms;

- polarisation of M1 macrophages;

- ROS production;

- production of pro-inflammatory cytokines;

- bone resorption

 [106, 107] [44, 64, 87, 88]
  DKK-1

- bone remodelling;

- joint degradation;

- chondrocyte ageing

 [108–110] [64, 76, 91]
  IL6

- induction of the expression of ICAM-1;

- downregulation of type II collagen expression;

- pro-inflammatory influence;

- production of B lymphocytes;

- production of antibodies;

- bone homeostasis;

- differentiation of osteoclast;

- pathogenesis of vascular inflammation;

- the balance between the modulation of MMPs and TIMPs

 [98, 111–114] [44, 46, 75, 76, 88, 90]
  IL10

- inhibition of inflammation markers;

- upregulation of IL-1Ra and TIMP;

- chondroprotection;

- reduction of apoptosis of cartilage tissue cells

 [111, 115, 116] [44, 87, 88]
  SDF-1

- induction of chondrocyte apoptosis;

- increase in the inflammatory process in OA;

- increase in the expression of IL-1, TNFα and MMPs;

- reduction in the expression of COL2 and ACAN

 [117–120] [21, 44, 64]
Lipids
  PGE2

- stimulation of IL-10 production;

- reduction of apoptosis in hepatocytes;

- downregulation of the expression of SERPINE1/ PAI-1;

- reduction in the expression of ACAN;

- secretion of plasmin activator;

- promotion of extracellular matrix degradation

 [64, 82, 86, 121] [40, 64, 86]
  SEA - downregulation of the expression of pro-inflammatory factors [64, 122] [64]

ACAN aggrecan, CCL2 C–C motif chemokine ligand 2, COL2 collagen type II, COMP cartilage oligomeric matrix protein, DKK-1 dickkopf 1, ECM extracellular matrix, FGF fibroblast growth factor, HGF hepatocyte growth factor, ICAM-1 intercellular adhesion molecule-1, IFN-γ interferon γ, IL-1Ra interleukin-1 receptor antagonist, IL-1 /-6 /-10 interleukin 1 /6 /10, LIF leukemia inhibitory factor, MMPs matrix metalloproteinases, MPCs mesenchymal chondro-progenitor cells, OA osteoarthritis, PAI plasminogen activator inhibitor, PDGF platelet derived growth factor, PGE2 prostaglandin-E2, ROS reactive oxygen species, SDF-1 stromal cell-derived factor 1, SEA N-stearoylethanolamide, SERPINE serine proteinase inhibitor, TGF-β transforming growth factor β, TIMP-1 /-2 tissue inhibitor of metalloproteinases-1 /-2, TNFα tumour necrosis factor α, VEGF vascular endothelial growth factor, VIM vimentin