Disease relevance of CILP

• All 4 mice strains, DBA/1J, ICR, C57BL/6, and BALB/c, immunized with the CILP fusion proteins developed chronic arthritis; in particular, the ICR mice developed polyarthritis that was characterized by infiltration of mononuclear cells in the synovium and exfoliation of the surface of cartilage [1].
• CILP is implicated in common musculoskeletal disorders, including osteoarthritis and lumbar disc disease [2].
• The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes [3].
• Exclusion of the gene for human cartilage intermediate layer protein in currently mapped calcium pyrophosphate dihydrate deposition syndromes [4].

High impact information on CILP

• CILP colocalized with TGF-beta1 in clustering chondrocytes and their territorial matrices in intervertebral discs [5].
• CILP was expressed abundantly in intervertebral discs, and its expression increased as disc degeneration progressed [5].
• Using a case-control association study, we identified a functional SNP (1184T --> C, resulting in the amino acid substitution I395T) in CILP, which encodes the cartilage intermediate layer protein, that acts as a modulator of LDD susceptibility [5].
• The same ADAM12 haplotype (OR 2.54 [95% CI 1.2-5.4]) and a haplotype in the CILP gene (OR 0.38 [95% CI 0.23-0.62]) were the strongest associations in men [6].
• OBJECTIVE: Autoimmunity to proteins, such as type II collagen and cartilage intermediate layer protein, that are produced by chondrocytes has been reported in patients with osteoarthritis (OA) as well as in patients with rheumatoid arthritis (RA) [7].

Biological context of CILP

• Cloning and deduced amino acid sequence of a novel cartilage protein (CILP) identifies a proform including a nucleotide pyrophosphohydrolase [8].
• The amino-terminal half corresponds to CILP (molecular mass of 78.5 kDa, not including post-translational modifications) and the carboxyl-terminal half corresponds to a protein homologous to a porcine nucleotide pyrophosphohydrolase, NTPPHase (molecular mass of 51.8 kDa, not including post-translational modifications) [8].
• The CILP gene was mapped to human chromosome 15q22 [9].
• Southern blot analysis indicated a single copy of the CILP gene in the human genome [9].
• The investigation reported here revealed that the CILP gene consists of nine exons spanning approximately 15 kb of genomic DNA on chromosome 15q22 [10].

Anatomical context of CILP

• A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age [11].
• CONCLUSIONS: The results show that multiple T cell epitopes are needed for the development of CILP-induced arthritis, and present the characteristic new model of mild arthropathy accompanied by extra-articular calcifications [12].
• Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease [13].
• In addition, it was revealed that the cartilage intermediate layer protein immunization of mice developed calcification of tendons, thus indicating that autoimmunity modulates functions of target molecules [14].

Associations of CILP with chemical compounds

• In addition, mice were immunized with a mixture of the C1 and C2 fusion proteins to assess the arthrogenicity of CILP [1].
• We also find one repeat of this Cys domain in human cartilage intermediate layer protein but find no evidence of this domain in any invertebrate species, including those for which entire genomes have been sequenced [15].
• Administration of PPA produced a statistically significant increase in MUP and CILPP [16].

Regulatory relationships of CILP

• We have found that CILP mRNA expression is induced by TGF-beta1 and dependent upon signaling via TGF-beta receptors [2].

Other interactions of CILP

• Pathways other than Smad3 also are involved in TGF-beta1 induction of CILP [2].
• Cartilage intermediate layer protein (CILP) is an extracellular matrix protein abundant in cartilaginous tissues [2].
• Implication of cartilage intermediate layer protein in cartilage destruction in subsets of patients with osteoarthritis and rheumatoid arthritis [1].
• METHODS: Using primary cultures of articular chondrocytes from the knee, we defined the function of the previously described CILP (CILP-1) and of a recently described 50.6% identical protein that we designated the CILP-2 isoform [17].
• Other molecules, such as the cartilage-derived C-type lectin and cartilage intermediate layer protein have no role as yet [18].

Analytical, diagnostic and therapeutic context of CILP

• Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK [13].
• METHODS: A radiation hybrid panel was analyzed for chromosomal assignment of the CILP gene within a 1-cM limit of resolution [4].

References