Markers Expressed in LSJL:
Aggrecan
COL2A1
Col9a1
Col9a3
Col10a1
Sox9
Additional markers are listed here:
Regulation of chondrogenesis and chondrocyte differentiation by stress
"During this early step in chondrogenesis, the condensing mesenchyme expresses various ECM and cell adhesion molecules, including the IIa splice form of type II collagen [Col2a1(IIa)], N-cadherin (Ncad), N-cam (Ncam1), and tenascin C (Tnc){down}, while also broadly expressing an important transcription factor, SRY-box 9 (Sox9) "
"As the mesenchyme differentiates into chondrocytes, the cells begin to produce an ECM rich in the IIb splice form of type II collagen [Col2a1(IIb)] and aggrecan (Agc)."
"The flat columnar chondrocytes, known to be the most proliferative cells in the cartilage element, express low levels of Runx2 and Osterix (Osx) and high levels of Fgfr3, Nkx3.2{a possible related gene is down in LSJL}, and Ptc1. "
"The prehypertrophic chondrocytes enlarge slightly and initiate expression of Ihh, parathyroid hormone–related protein receptor (PTHrP-R), as well as increase expression of alkaline phosphatase (AP), and the important regulatory transcription factors Runx2 and Osx, which aid in chondrocyte differentiation as well as being required for mineralization of the cartilage"
"As hypertrophy proceeds, the cells continue to enlarge, generate a mineralized matrix, and further enhance their expression of type X collagen (Col10a1){up}, Runx2, and several growth factors that coordinate chondrocyte proliferation and differentiation."
"Both hypertrophic chondrocytes and the more terminally differentiated hypertrophic chondrocytes located in the center of the cartilage produce high levels of Vegfa, which is thought to aid in vascularization of the dying cartilage. Only the most terminally differentiated hypertrophic chondrocytes express the matrix degrading enzyme Mmp13. MMP13 is an enzyme that controls degradation of the cartilage matrix, a process that precedes mineralization by osteoblasts, that is required for creation of the bone marrow space, and that supports vascular invasion, which provides the cells that will populate the bone marrow"
"activation of proline-rich tyrosine kinase 2 (Pyk2), leading to the upregulation of collagenase III{MMP3 is up in LSJL} expression via PKC following exposure to fibronectin fragments"
"cytoskeletal elements control opening and closing of VGCCs in neuronal cells, a similar regulatory paradigm might exist in chondrocytes. Thus, transfer of mechanical stress through the cytoskeleton could induce opening of these channels, the propagation of intracellular calcium waves, and the subsequent induction of phenotypic effects in the cells. In general, calcium transients lead to activation of signaling via both calmodulin kinase and calcineurin/NFAT pathways"
"inhibition of COX-2–dependent stimulation of PGE2 production from human bone marrow–derived MSCs using NS-398 suppresses expression of BMP-2 "
"levels of exposure to Pb during childhood are inversely correlated with final height, weight, and chest circumference"
"Pb-exposed micromass cultures of primary limb bud MSCs have increased Sox9 and Col2 expression as well as cartilage nodule formation. Pb causes pathway-specific effects on these cells, including enhanced phosphorylation of the TGF-β–specific Smads (Smad2 and Smad3) and decreased phosphorylation of the BMP-2–specific Smads (Smad1, Smad5, and Smad8)"
"during the endochondral ossification phase of ectopic bone formation in this model, Pb inhibits chondrocyte maturation"
"Cadmium induces apoptosis of mesenchymal populations adjacent to the apical ectodermal ridge, reducing the cartilage-forming potential of the tissue in the developing limb. Similarly, quantum dots comprised of a combination of cadmium, selenium, and zinc inhibit chondrogenesis in bone marrow progenitors "
"Zinc was found to have a biphasic effect on chondrocyte differentiation, with low doses inducing AP activity and high doses inhibiting mineralization. Comparatively, manganese caused a reduction of mineralization, whereas the effects of cadmium were acutely toxic "
Microarray Analyses of Gene Expression during Chondrocyte Differentiation Identifies Novel Regulators of Hypertrophy
"Overexpression of Rgs2 in the chondrogenic cell line ATDC5 resulted in accelerated hypertrophic differentiation"
"ATF-2 controls cell cycle progression and proliferation"
"well-characterized markers of chondrocyte differentiation [include] Sox9 and Ibsp{up in LSJL as BSP at 1 week}"
" Sox9 mRNA showed peak expression during days 3 and 6 of the culture period, after which transcript levels decreased by 50% in parallel with the maturation of differentiated chondrocytes. The opposite pattern was observed for Ibsp transcripts, which showed very low expression until days 12 and 15 of culture when cartilage cells terminally differentiate and up-regulate Ibsp mRNA levels 1200-fold." This is consistent with LSJL where expression of BSP did not increase until 1 week after the third loading.
IGFBP6 which is mentioned as a chondrogenic end stage marker is upregulated in LSJL.
Genes that tended to be co-expressed:
Cluster 1:
COMP
BSP{up at 1 week}
MMP13
WISP2{up}
Sod3{up}
C1r{down}
Adh7{up}
So this provides evidence that LSJL induced an increase in COMP the pro-chondrogenic gene.
Cluster2:
Col14a1{up}
Col12a1{up}
BC020108{up in LSJL as ARSI}
Mglap
Cluster3:
BMP7
Pdlim3{up}
Art1{down}
"MPCs could differentiate specifically into osteoblasts when treated with dexamethasone, ascorbic acid, and β-glycerophosphate, and chondroblasts when treated with TGF-β I."
"some TFs up-regulated during chondroblast differentiation on day 7, such as PAX-8 and HOXD4"
"MSX-2 transcripts were up-regulated >2-fold from day 2 on in chondroblast cultures, but not until day 7 in osteoblasts"
Genes upregulated during osteoblast differentiation that were up(or-down regulated during LSJL) and were either unchanged or suppressed during chondrogenic differentiation:
MTF1{down}
Genes upregulated doing chondrogenic differentiation that were up(or -down regulated during LSJL) but were unchanged or suppressed during osteoblast differentiation:
TCF7{down}
Jun
-------Different cluster
Zfp9
Genes downregulated in chondrogenic and/or osteogenic differentiation and in LSJL:
CA150
Egr1{up}
XBP1
SSBP1
BTF3
nr4a2{up}
Genes upregulated in chondro and/or osteo differentiation:
Mef2d{down}
zfp36
Genes upregulated at different times between osteoblasts and chondrocytes also up in LSJL:
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