In homozygous mice, we observed a dwarf phenotype, which persisted throughout adulthood supporting the evidence that reduced aggrecan amount impairs skeletal growth.
However, eight additional horses with dwarfism were found, seven of which were heterozygotes for D2, D3* or D4, suggesting the existence of additional ACAN alleles causing dwarfism.
A novel ACAN gene variant c.7465 T > C (p. Gln2364Pro), predicted to be disease causing, was discovered in the children, without evident syndromic short stature; mild bone abnormity was present in these children, including cervical-vertebral clefts and apophyses in the upper and lower thoracic vertebrae.
Cynomolgus macaques were immunized with four citrullinated peptides from vimentin, fibrinogen, and aggrecan, known to induce T-cell response in RA patients, and received an intra-articular (IA) boost with the same four citrullinated peptides pooled.
Whole-exome sequencing identified a novel heterozygous frameshift mutation in the ACAN gene (c.1744delT; p.Phe582fs*69) in all of the affected family members but not in the unaffected one, providing further evidence that ACAN haploinsufficiency causes short stature with advanced bone maturation.
To ascertain the prevalence of ACAN mutations and broaden the phenotypic spectrum in patients with idiopathic short stature we performed sequence analyses in 428 families.
Mutations in the ACAN gene should be included in the differential diagnosis of the child with idiopathic short stature or familial short stature and bone age advancement.
An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats.
Our findings thus expand the spectrum of ACAN defects and provide a new molecular genetic etiology for the unusual child who presents with short stature and accelerated skeletal maturation.
ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) degrades aggrecan, the primary component of cartilage, therefore contributing to joint erosion in RA.
Patients with early RA were more likely to produce IL-6 in response to no epitope or to citrullinated aggrecan, while patients with longstanding RA were more likely to produce IL-6 to more than one epitope.
To identify a biomarker for prediction of the response to infliximab (IFX) in patients with rheumatoid arthritis (RA), we focused on a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) that seems to play a key role in aggrecan degradation in cartilage.
Five loci (SPAG17, KBTBD8, HHIP, HIST1H1D and ACAN) were significantly associated with ISS (uncorrected P<0.05), indicating that height-associated genes in the adult population are involved in extreme cases of short stature in children.
Osteoarthritic (OA) cartilage degeneration and cartilage destruction in rheumatoid arthritis depends significantly on enzymatic degradation of cartilage proteoglycan aggrecan.