ArticleOsteoarthritis and cartilage2018
Mutations in osteoprotegerin account for the CCAL1 locus in calcium pyrophosphate deposition disease.
Article in Osteoarthritis and cartilage, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- A novel murine model of early calcium pyrophosphate deposition disease based on the TNFRSF11B mutation mimics features of the human disease.Annals of the rheumatic diseases · 2026Article
- Ultrasonography in the assessment of calcium pyrophosphate deposition disease.Skeletal radiology · 2025Review
- Architecture mechanics mediated osteogenic progression in bone regeneration of artificial scaffolds.Science advances · 2025Article
- Features Associated With Different Inflammatory Phenotypes of Calcium Pyrophosphate Deposition Disease: A Study Using Data From the International American College of Rheumatology/EULAR Calcium Pyrophosphate Deposition Classification Criteria Cohort.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Calcium Pyrophosphate Crystal Formation and Deposition: Where Do we Stand and What Does the Future hold?Current rheumatology reports · 2024Review
- Calcium pyrophosphate deposition disease: historical overview and potential gaps.Frontiers in medicine · 2024Review
- Mutation in the CCAL1 locus accounts for bidirectional process of human subchondral bone turnover and cartilage mineralization.Rheumatology (Oxford, England) · 2022Article
- Biochemical characterization of a disease-causing human osteoprotegerin variant.Scientific reports · 2022Article
- The role of TNFRSF11B in development of osteoarthritic cartilage.Rheumatology (Oxford, England) · 2022Article
- Identification of Common Pathogenic Pathways Involved in Hemochromatosis Arthritis and Calcium Pyrophosphate Deposition Disease: a Review.Current rheumatology reports · 2022Review
- "Lessons from Rare Forms of Osteoarthritis".Calcified tissue international · 2021Review
- Effects of the TNFRSF11B Mutation Associated With Calcium Pyrophosphate Deposition Disease in Osteoclastogenesis in a Murine Model.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Collagen networks within 3D PEG hydrogels support valvular interstitial cell matrix mineralization.Acta biomaterialia · 2021Article
- CCAL1 enhances osteoarthritis through the NF-κB/AMPK signaling pathway.FEBS open bio · 2020Article
- Interleukin-1 Blockade in Polygenic Autoinflammatory Disorders: Where Are We now?Frontiers in pharmacology · 2020Review
- BONE MARKERS IN ARTHROPATHIES.Acta clinica Croatica · 2019Review
- Omnipresence of inflammasome activities in inflammatory bone diseases.Seminars in immunopathology · 2019Review
- Calcium crystal deposition diseases - beyond gout.Nature reviews. Rheumatology · 2018Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveMutations on chromosomes 5p (CCAL2) and 8q (CCAL1) have been linked to familial forms of calcium pyrophosphate deposition disease (CPDD). Mutations in the ANKH gene account for CCAL2, but the identity of CCAL1 has been elusive. Recently, a single Dutch kindred with a mutation in the Tumor Necrosis Factor Receptor Super Family member 11B (TNFRSF11B) gene coding for osteoprotegerin (OPG) was described as a gain-of-function mutation. Affected family members had premature generalized osteoarthritis (PGOA) and CPDD. As the TNFRSF11B gene is on 8q, we sought additional evidence that TNFRSF11B was CCAL1, and investigated potential disease mechanisms.
designDNA from two novel PGOA/CPDD families was screened for sequence variants in the TNFRSF11B gene. Mutations were verified by genotype analysis of affected and unaffected family members. We also investigated effects of normal and mutant OPG on regulators of CPP crystal formation in porcine cartilage.
resultsThe identical TNFRSF11B mutation described in the Dutch family was present in two novel PGOA/CPDD families. ANKH was normal in affected patient fibroblasts. Exogenous OPG did not alter ANKH mRNA or protein levels, affect translocation of ANKH to the membrane, nor increase [pyrophosphate (PPi)] or other key regulators of CPDD.
conclusionWe have firmly established the identity of CCAL1 as TNFRSF11B (OPG). Our findings suggest that this mutation produces disease in an ANKH-independent manner via novel mechanisms not primarily targeting cartilage. This work rationalizes further investigation of OPG pathway components as potential druggable targets for CPDD.
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