1. Regulation of senescence associated signaling mechanisms in chondrocytes for cartilage tissue regeneration 
S. Ashraf, B.-H. Cha, J.-S. Kim, J. Ahn, I. Han, H. Park, S.-H. Lee 
Osteoarthritis and Cartilage 
Volume 24, Issue 2, Pages (February 2016)
DOI: /j.joca
Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

2. Fig. 1
Cellular senescence and dedifferentiation in chondrocytes. (A) Chondrocytes serially cultured in monolayer and their morphology changed from polygonal in P2 to fibroblastic in P6 that reveal the dedifferentiated cells. (B) mRNA expression analysis of Col II and Col X in P2 and P6 chondrocytes by RT-PCR. (C) Senescence observed by SA-β Galactosidase assay also shows more positive senescent cells in P6. The blue color indicates the positive senescent cells. (D) DIC images of normal chondrocytes and degenerated chondrocytes isolated from normal cartilage and OA cartilage respectively. (E) Col I observation by western blotting in normal (N) and degenerated (D) chondrocytes. (F) DIC images of normal nucleus pulpous chondrocytes (NPC) and dNPC isolated from normal cartilage and OA cartilage respectively. (G) Left panel shows Alcian blue staining of NPC and dNPC. The right panel shows Alcian blue staining extraction of NPC and dNPC. (Scale bar = 100 μm, n = 3, *P < 0.05).
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

3. Fig. 2
Genes involved in the maintenance of normal phenotypic chondrocytes and can regenerate cartilage. Chondrocytes isolated from normal articular cartilage can regenerate cartilage again after expansion in monolayer culture if followed the signaling mechanism of IGF-1, TGB-β and BMP-2. IGF-1, TGB-β and BMP-2 ultimately involved in the formation of GAG matrix required for maintaining chondrocytes normal phenotype and molecular functions. Inhibition or down regulation of IGF-1, TGF-β, BMP-2 and especially Sox9 cause senescence in the chondrocytes. Sox9 seems to be a major regulator of controlling senescence in chondrocyte via maintaining chondrocytes normal phenotype/morphology through Col2a1, core protein and aggrecan (For further details please see the text).
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

4. Fig. 3
Genes directly involved in cellular senescence and dedifferentiation of chondrocytes during prolonged in vitro monolayer culture. ROS are a main cause of senescence and regulator of genes responsible for senescence. Among all genes, IL-1β and p38 MAPK are two main genes which further activate multiple pathways to induce senescence and dedifferentiation (For more details please see the text).
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

5. Fig. 4
Schematic illustration of discrete genes expression in normal and senescent chondrocytes. Genes mentioned in upper green arrow responsible for maintenance of normal phenotypic chondrocytes and their down regulation lead towards senescent chondrocytes. Genes mentioned in red arrow responsible for senescence and their expression up regulated when normal chondrocytes shift towards senescent chondrocytes.
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions