1. are dispersed within matrix nonuniformly
1.1. under physiological conditions
1.1.1. cell duplexes
1.1.2. cellular columns
1.2. under pathological conditions
1.2.1. dense cellular clasters
1.2.1.1. 'Cartilage cell clusters' [Lotz et al., 2010]
2. are cells observed in articular hyaline cartilage
2.1. 'The Basic Science of Articular Cartilage' [Fox et al., 2009]
3. express
3.1. phenotype markers
3.1.1. secreted
3.1.1.1. aggrecan
3.1.1.1.1. properties
3.1.1.1.2. expression
3.1.1.2. aggrecanase
3.1.1.2.1. two isoforms
3.1.1.3. angiopoietin-like 4
3.1.1.3.1. vascular growth factor, can control lipid metabolism
3.1.1.3.2. expression
3.1.1.4. collagens
3.1.1.4.1. Col2a1
3.1.1.4.2. Col10a1
3.1.1.5. collagenase-1
3.1.1.5.1. expression
3.1.1.6. matrix metalloproteinases (MMPs)
3.1.1.6.1. are involved in collagen maturation
3.1.1.6.2. MMP-1
3.1.1.6.3. MMP-2
3.1.1.6.4. MMP-3
3.1.1.6.5. MMP-8
3.1.1.6.6. MMP-9
3.1.1.6.7. MMP-13
3.1.1.7. tissue inhibitor of metalloproteinases
3.1.1.7.1. TIMP-1
3.1.1.7.2. TIMP-3
3.1.2. intracellular
3.1.2.1. Runx2
3.1.2.1.1. properties
3.1.2.1.2. facts from
3.1.2.1.3. expression
3.1.2.2. SRY-box 9 (Sox9)
3.1.2.2.1. properties
3.1.2.2.2. facts from
3.1.2.2.3. expression
3.2. surface markers
3.2.1. integrins
3.2.1.1. multiple variants
3.2.1.1.1. different patterns in normal and pathological cells
3.2.1.1.2. involved in mechanotransduction
3.2.1.2. beta1
3.2.1.2.1. properties
3.2.1.2.2. facts from
3.2.1.2.3. expression
3.3. state markers
3.3.1. for apoptosis
3.3.1.1. caspase-3
3.3.1.1.1. effector (or executioner, or downstream) caspase
3.3.1.1.2. facts from
3.3.1.1.3. expression
3.3.1.1.4. activity
3.3.1.1.5. properties
3.3.2. for oxidative stress
3.3.2.1. catalase
3.3.2.1.1. antioxidant enzyme that decomposes hydrogen peroxide
3.3.2.1.2. facts from
3.3.2.1.3. activity
3.3.2.2. glutathione reductase
3.3.2.2.1. antioxidant enzyme needed to recycle reduced form of glutathione
3.3.2.2.2. facts from
3.3.2.2.3. activity
3.3.2.3. thioredoxin reductase
3.3.2.3.1. a family of antioxidant enzymes
3.3.2.3.2. activity
3.3.3. for survival
3.3.3.1. Bcl-2
3.3.3.1.1. apoptosis supressor
3.3.3.1.2. facts from
3.3.3.1.3. expression
3.3.3.2. SirT1
3.3.3.2.1. protein deacetylase
3.3.3.2.2. presence of inactive cleaved SirT1 variant (75 SirT1; 75 kDa) is associated with improved articular chondrocyte survival
4. Conditions
4.1. Apoptosis
4.1.1. stimulates
4.1.1.1. caspase-3 activity
4.1.1.1.1. by IL-1beta
4.2. Chondrocytes aggregation
4.2.1. due to hyaluronic acid degradation
4.2.1.1. suppresses
4.2.1.1.1. apoptosis
4.3. Hypoxia
4.3.1. stimulates
4.3.1.1. Angiopoietin-like 4 expression and secretion
4.3.1.1.1. 'Hypoxia upregulates the expression of angiopoietin-like-4 in human articular chondrocytes: role of angiopoietin-like-4 in the expression of matrix metalloproteinases and cartilage degradation' [Murata et al., 2009]
4.3.1.2. Col2a1 expression
4.3.1.2.1. in culture
4.3.1.3. Sox9 expression
4.3.1.3.1. 'Hypoxia induces chondrocyte-specific gene expression in mesenchymal cells in association with transcriptional activation of Sox9' [Robins et al., 2005]
4.3.1.3.2. 'Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect' [Lee et al., 2013]
4.3.2. suppresses
4.3.2.1. Col10a1 expression
4.3.2.1.1. in culture
4.4. Osteoarthritis development
4.4.1. stimulates
4.4.1.1. MMP-9 expression/activity (in IL-1β-independent manner)
4.4.1.1.1. 'MMP-9/gelatinase B is a gene product of human adult articular chondrocytes and increased in osteoarthritic cartilage' [Söder et al., 2006]
5. Intrinsic regulatory factors
5.1. Angiopoietin-like 4
5.1.1. stimulates
5.1.1.1. MMP-1 and MMP-3 expression
5.1.1.1.1. 'Hypoxia upregulates the expression of angiopoietin-like-4 in human articular chondrocytes: role of angiopoietin-like-4 in the expression of matrix metalloproteinases and cartilage degradation' [Murata et al., 2009]
5.2. Collagen
5.2.1. suppresses
5.2.1.1. apoptosis
5.2.1.1.1. via β1-collagen interaction
5.3. Collagen degradation products
5.3.1. stimulates
5.3.1.1. MMP-2, MMP-3, MMP-9, and MMP-13 expression
5.3.1.1.1. 'Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes' [Fichter et al., 2006]
5.4. Histamine
5.4.1. stimulates
5.4.1.1. chondocyte proliferation
5.4.1.1.1. 'Histamine stimulates the proliferation of human articular chondrocytes in vitro and is expressed by chondrocytes in osteoarthritic cartilage' [Tetlow, Woolley, 2003]
5.4.1.2. MMP-3 and MMP-13 expression
5.4.1.2.1. 'Histamine stimulates matrix metalloproteinase-3 and -13 production by human articular chondrocytes in vitro' [Tetlow, Woolley, 2002]
5.5. IGF-1 (insulin-like growth factor 1)
5.5.1. suppresses
5.5.1.1. MMP-1 and MMP-8 expression and activity
5.5.1.1.1. 'IGF and IGF-binding protein system in the synovial fluid of osteoarthritic and rheumatoid arthritic patients' [Tavera et al., 1996]
5.5.2. action mediated by
5.5.2.1. protein kinases C
5.5.2.1.1. 'Regulation of chondrogenesis by protein kinase C: Emerging new roles in calcium signalling' [Matta, Mobasheri, 2014]
5.6. Interleukin-1β
5.6.1. stimulates
5.6.1.1. caspase-3 activity
5.6.1.1.1. 'Resveratrol inhibits IL-1 beta-induced stimulation of caspase-3 and cleavage of PARP in human articular chondrocytes in vitro' [Shakibaei et al., 2007]
5.6.1.1.2. 'Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study' [Shakibaei et al., 2005]
5.6.2. suppresses
5.6.2.1. collagen II synthesis
5.6.2.1.1. 'Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study' [Shakibaei et al., 2005]
5.6.2.2. integrin beta-1 expression
5.6.2.2.1. 'Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study' [Shakibaei et al., 2005]
5.6.2.3. death receptor (CD95) activation
5.6.2.3.1. 'IL-1 beta protects human chondrocytes from CD95-induced apoptosis' [Kühn et al., 2000]
5.7. Interleukin-4
5.7.1. stimulates
5.7.1.1. aggrecan expression (in normal chondrocytes only)
5.7.1.1.1. 'Mechanotransduction via integrins and interleukin-4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes' [Millward-Sadler et al., 2000]
5.7.1.1.2. 'Extracellular and intracellular mechanisms of mechanotransduction in three-dimensionally embedded rat chondrocytes' [Shioji et al., 2012]
5.7.1.2. collagen II expression
5.7.1.2.1. 'Extracellular and intracellular mechanisms of mechanotransduction in three-dimensionally embedded rat chondrocytes' [Shioji et al., 2012]
5.7.2. suppresses
5.7.2.1. MMP-3 expression (in normal chondrocytes only)
5.7.2.1.1. 'Mechanotransduction via integrins and interleukin-4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes' [Millward-Sadler et al., 2000]
5.8. Interleukin-18
5.8.1. stimulates
5.8.1.1. aggrecanase-2 expression
5.8.1.1.1. 'Implication of interleukin 18 in production of matrix metalloproteinases in articular chondrocytes in arthritis: direct effect on chondrocytes may not be pivotal' [Dai et al., 2005]
5.8.1.2. caspase-3 activity
5.8.1.2.1. 'Interleukin-18 induces apoptosis in human articular chondrocytes' [John et al., 2007]
5.8.1.3. MMP-1, MMP-3 and MMP-13 expression
5.8.1.3.1. 'Implication of interleukin 18 in production of matrix metalloproteinases in articular chondrocytes in arthritis: direct effect on chondrocytes may not be pivotal' [Dai et al., 2005]
5.8.1.4. TIMP-1 expression
5.8.1.4.1. 'Implication of interleukin 18 in production of matrix metalloproteinases in articular chondrocytes in arthritis: direct effect on chondrocytes may not be pivotal' [Dai et al., 2005]
5.9. EGF (epidermal growth factor)
5.9.1. action mediated by
5.9.1.1. protein kinases C
5.9.1.1.1. 'Regulation of chondrogenesis by protein kinase C: Emerging new roles in calcium signalling' [Matta, Mobasheri, 2014]
5.10. Nitric oxide (NO)
5.10.1. induces
5.10.1.1. chondrogenic differentiation
5.10.1.1.1. 'Neural crest development and craniofacial morphogenesis is coordinated by nitric oxide and histone acetylation' [Kong et al., 2014]
5.10.1.2. apoptosis and cartilage degeneration
5.10.1.2.1. 'ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status' [Kim et al., 2002]
5.10.2. stimulates
5.10.2.1. caspase-3 activity
5.10.2.1.1. 'The induction of cell death in human osteoarthritis chondrocytes by nitric oxide is related to the production of prostaglandin E2 via the induction of cyclooxygenase-2' [Notoya et al., 2000]
5.10.2.1.2. 'ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status' [Kim et al., 2002]
5.10.2.1.3. 'Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes' [Wu et al., 2007]
5.10.3. doesn't influence
5.10.3.1. catalase activity
5.10.3.1.1. 'Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels' [Carlo, Loeser, 2003]
5.10.4. suppresses
5.10.4.1. Bcl-2 expression
5.10.4.1.1. 'The induction of cell death in human osteoarthritis chondrocytes by nitric oxide is related to the production of prostaglandin E2 via the induction of cyclooxygenase-2' [Notoya et al., 2000]
5.10.4.2. glutathione reductase activity
5.10.4.2.1. 'Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels' [Carlo, Loeser, 2003]
5.10.4.3. thioredoxin reductase activity
5.10.4.3.1. 'Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels' [Carlo, Loeser, 2003]
5.11. Oncostatin M
5.11.1. stimulates
5.11.1.1. collagenase-1 expression
5.11.1.1.1. 'Oncostatin M up-regulates tissue inhibitor of metalloproteinases-3 gene expression in articular chondrocytes via de novo transcription, protein synthesis, and tyrosine kinase- and mitogen-activated protein kinase-dependent mechanisms' [Li, Zafarullah, 1998]
5.11.1.2. TIMP-1 expression
5.11.1.2.1. 'Stimulation of TIMP-1 production by oncostatin M in human articular cartilage' [Nemoto et al., 1996]
5.11.1.3. TIMP-3 expression
5.11.1.3.1. 'Oncostatin M up-regulates tissue inhibitor of metalloproteinases-3 gene expression in articular chondrocytes via de novo transcription, protein synthesis, and tyrosine kinase- and mitogen-activated protein kinase-dependent mechanisms' [Li, Zafarullah, 1998]
5.12. TGF-β
5.12.1. blocks
5.12.1.1. hypertrophic (stage II) chondrocyte differentiation
5.12.1.1.1. 'Cartilage biology in osteoarthritis--lessons from developmental biology' [Pitsillides, Beier, 2011]
5.12.2. stimulates
5.12.2.1. TIMP-3 expression
5.12.2.1.1. 'Up-regulation of tissue inhibitor of metalloproteinases-3 gene expression by TGF-beta in articular chondrocytes is mediated by serine/threonine and tyrosine kinases' [Su et al., 1998]
5.13. Tumor necrosis factor α (TNF-α)
5.13.1. stimulates
5.13.1.1. caspase-3 activity
5.13.1.1.1. 'The ECM-cell interaction of cartilage extracellular matrix on chondrocytes' [Gao et al., 2014]
6. Xenobiotics
6.1. Curcumin
6.1.1. stimulates
6.1.1.1. collagen II synthesis
6.1.1.1.1. 'Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study' [Shakibaei et al., 2005]
6.1.1.2. beta1-integrin expression
6.1.1.2.1. 'Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study' [Shakibaei et al., 2005]
6.1.2. suppresses
6.1.2.1. caspase-3 activation
6.1.2.1.1. 'Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study' [Shakibaei et al., 2005]
6.2. Statins
6.2.1. suppresses
6.2.1.1. MMP-3 production induced by IL-1β
6.2.1.1.1. 'Simvastatin reduces MMP-3 level in interleukin 1beta stimulated human chondrocyte culture' [Lazzerini et al., 2004]
6.2.1.2. MMP-3 and MMP-9 production induced by IL-1β
6.2.1.2.1. 'Pravastatin suppresses matrix metalloproteinase expression and activity in human articular chondrocytes stimulated by interleukin-1β' [Baker et al., 2012]
6.2.1.3. MMP-13 production induced by IL-1β
6.2.1.3.1. 'Protective effect of atorvastatin in cultured osteoarthritic chondrocytes' [Simopoulou et al., 2010]
6.3. Pycnogenol
6.3.1. suppresses
6.3.1.1. MMP-9 production induced by IL-1β
6.3.1.1.1. 'Pycnogenol attenuates cyclooxygenase 2 and matrix metalloproteinase 9 in articular chondrocytes induced by interleukin-1beta' [Lee, Peng, 2012]
6.4. Resveratrol
6.4.1. suppresses
6.4.1.1. caspase-3 activation
6.4.1.1.1. 'Resveratrol inhibits IL-1 beta-induced stimulation of caspase-3 and cleavage of PARP in human articular chondrocytes in vitro' [Shakibaei et al., 2007]