EMAIL THIS PAGE TO A FRIEND

Osteoarthritis and cartilage

Liver X Receptor activation delays chondrocyte hypertrophy during endochondral bone growth.


PMID 24852699

Abstract

Activation of the Liver X Receptor (LXR) has recently been identified as a therapeutic strategy for osteoarthritis (OA). Human OA articular cartilage explants show decreased LXR expression, and LXRβ-null mice display OA-like symptoms. LXR agonist administration to OA articular cartilage explants suppresses proteoglycan degradation and restores LXR-activated transcription. We aimed to investigate the effect of LXR activation on chondrocyte differentiation to elucidate the molecular mechanisms behind its protection against OA. The specific LXR agonist, GW3965, was used to examine the effect of LXR activation on chondrocyte differentiation. Tibia organ cultures were used to examine the effect of LXR activation on bone growth and growth plate morphology, followed by immunohistochemical analysis. In ATDC5 and micromass cultures, chondrocyte differentiation was examined through cellular staining and proliferation assays. Various chondrogenic markers were analyzed by real-time reverse-transcription polymerase chain reaction (qRT-PCR) in micromass RNA. Chondrocyte hypertrophy was suppressed by GW3965 treatment, as shown by decreased hypertrophic zone length in the tibial growth plate, decreased alkaline phosphatase staining in ATDC5 and micromass cultures, and down regulation of Col10a1, Mmp13 and Runx2 expression. Increased proliferation in treated ATDC5 cells and up-regulation of Col2a1 expression in treated micromass cultures suggest hypertrophy is suppressed secondary to prolonged proliferation. Decreased p57 levels in treated growth plates suggest this to be due to cell-cycle exit delay. Our findings regarding LXR's role in cartilage development provide insight into how LXR activation prevents cartilage breakdown, further solidifying its potential as a therapeutic target of OA.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

74440
(−)-Nopol, purum, ≥98.0% (sum of enantiomers, GC)
C11H18O
HPA002924
Anti-CDKN1C antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV34285
Anti-CORO1A (AB1) antibody produced in rabbit, IgG fraction of antiserum
AV38899
Anti-CORO1A (AB2) antibody produced in rabbit, IgG fraction of antiserum
AV38900
Anti-CORO1A (AB3) antibody produced in rabbit, IgG fraction of antiserum
AV34286
Anti-CORO1A antibody produced in rabbit, affinity isolated antibody
HPA051132
Anti-CORO1A antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB4200078
Anti-Coronin-1A (N-terminal) antibody produced in rabbit, ~1.5 mg/mL, affinity isolated antibody
SAB1300483
Anti-KIP2 (N-term) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
P0357 Anti-p57Kip2 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
PHR1553
Dimethylformamide, Pharmaceutical Secondary Standard; Certified Reference Material
C3H7NO
SAB5300325
Monoclonal Anti-CDKN1C antibody produced in mouse, clone 3E3, ascites fluid
WH0011151M1
Monoclonal Anti-CORO1A antibody produced in mouse, clone 4G10, purified immunoglobulin, buffered aqueous solution
D4551
N,N-Dimethylformamide, for molecular biology, ≥99%
C3H7NO
227056
N,N-Dimethylformamide, anhydrous, 99.8%
C3H7NO
648531
N,N-Dimethylformamide, for HPLC, ≥99.9%
C3H7NO
437573
N,N-Dimethylformamide, ACS reagent, ≥99.8%
C3H7NO
72438
N,N-Dimethylformamide, analytical standard
C3H7NO
209643
Selenium, pellets, <5 mm, ≥99.99% trace metals basis
Se
204307
Selenium, pellets, <5 mm particle size, ≥99.999% trace metals basis
Se
229865
Selenium, powder, −100 mesh, 99.99% trace metals basis
Se
209651
Selenium, powder, −100 mesh, ≥99.5% trace metals basis
Se
HT-SE101
Selenium, pellets, < 5mm, ≥99.999%
Se
GF66395212
Selenium, foil, 25x25mm, thickness 3mm, 99.95%
Se