Employing molecular genetics of chondrodysplasias to inform the study of osteoarthritis

Kannu, Peter; Bateman, John F.; Belluoccio, Daniele; Fosang, Amanda J.; Savarirayan, Ravi

doi:10.1002/art.24251

Cited by 44 publications

(41 citation statements)

References 70 publications

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“…Loss of joint function in osteoarthritis (OA) is strongly associated with net loss of aggrecan and collagen breakdown caused by an imbalance of ECM homeostasis (1). In addition, many inherited human chondrodysplasias involve disruption of cartilage matrix assembly or cell-matrix interactions, resulting in abnormal skeletal development and in some cases early onset cartilage degeneration (2,3).…”

Section: Molecular and Cellular Proteomics 9:1296 -1313 2010mentioning

confidence: 99%

Comprehensive Profiling of Cartilage Extracellular Matrix Formation and Maturation Using Sequential Extraction and Label-free Quantitative Proteomics

Wilson

Diseberg

Gordon

et al. 2010

Molecular & Cellular Proteomics

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Articular cartilage is indispensable for joint function but has limited capacity for self-repair. Engineering of neocartilage in vitro is therefore a major target for autologous cartilage repair in arthritis. Previous analysis of neocartilage has targeted cellular organization and specific molecular components. However, the complexity of extracellular matrix (ECM) development in neocartilage has not been investigated by proteomics. To redress this, we developed a mouse neocartilage culture system that produces a cartilaginous ECM. Differential analysis of the tissue proteome of 3-week neocartilage and 3-day postnatal mouse cartilage using solubility-based protein fractionation targeted components involved in neocartilage development, including ECM maturation. Initially, SDS-PAGE analysis of sequential extracts revealed the transition in protein solubility from a high proportion of readily soluble (NaCl-extracted) proteins in juvenile cartilage to a high proportion of poorly soluble (guanidine hydrochloride-extracted) proteins in neocartilage. Label-free quantitative mass spectrometry (LTQ-Orbitrap) and statistical analysis were then used to filter three significant protein groups: proteins enriched according to extraction condition, proteins differentially abundant between juvenile cartilage and neocartilage, and proteins with differential solubility properties between the two tissue types. Classification of proteins differentially abundant between NaCl and guanidine hydrochloride extracts (n ‫؍‬ 403) using bioinformatics revealed effective partitioning of readily soluble components from subunits of larger protein complexes. Proteins significantly enriched in neocartilage (n ‫؍‬ 78) included proteins previously not reported or with unknown function in cartilage (integrin-binding protein DEL1; coiled-coil domain-containing protein 80; emilin-1 and pigment epithelium derived factor). Proteins with differential extractability between juvenile cartilage and neocartilage included ECM components (nidogen-2, perlecan, collagen VI, matrilin-3, tenascin and thrombospondin-1), and the relationship between protein extractability and ECM ultrastructural organization was supported by electron microscopy. Additionally, one guanidine extract-specific neocartilage protein, protease nexin-1, was confirmed by immunohistochemistry as a novel component of developing articular cartilage in vivo. The extraction profile and matrix-associated immunostaining implicates protease nexin-1 in cartilage development in vitro and in vivo. Molecular & Cellular Proteomics 9:1296 -1313, 2010.The cartilage of the mammalian skeletal system has two distinct roles. The epiphyseal cartilage of the growth plate drives endochondral bone growth, and the hyaline cartilage at the weight-bearing surfaces of bones facilitates joint articulation. In both environments, chondrocyte-regulated production, assembly, and turnover of the extracellular matrix (ECM) 1 are essential for the tissue to withstand compressive forces and respond to mechanical loading. The m...

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Section: Molecular and Cellular Proteomics 9:1296 -1313 2010mentioning

confidence: 99%

Comprehensive Profiling of Cartilage Extracellular Matrix Formation and Maturation Using Sequential Extraction and Label-free Quantitative Proteomics

Wilson

Diseberg

Gordon

et al. 2010

Molecular & Cellular Proteomics

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“…A hip-specific phenotype without other skeletal changes has never before been described for C-propeptide mutations (Table I), but is well described in COL2A1 helical mutations [Unger et al, 2001b;Richards et al, 2002;Zankl et al, 2004Zankl et al, , 2005Nishimura et al, 2005;Kannu et al, 2009Kannu et al, , 2010. Hip disease in association with a ''spondlyloepiphyseal dysplasia like'' phenotype due to C propetide mutations is also well known [Nishimura et al, 2005].…”

Section: To the Editormentioning

confidence: 93%

Avascular necrosis of the femoral head due to a novel C propeptide mutation in COL2A1

Kannu

O’Rielly

Hyland

et al. 2011

American J of Med Genetics Pt A

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“…In this model, the ligation of the medial collateral ligament coupled with disruption of the meniscus from its anterior-medial attachment can reproducibly induce OA over a 3 month time period. There are rare cases of OA involving mutations of types II, IX and XI collagen (Li et al, 2007;Kannu et al, 2009). In addition, OA progression is also affected by pro-inflammatory factors such as prostaglandins, TNF-, interleukin-1, interleukin-6 and nitric oxide.…”

Section: Genetic Contribution To Osteoarthritismentioning

confidence: 99%

Genetic Mouse Models for Osteoarthritis Research

Shen¹,

Wang²,

Jin³

et al. 2012

Principles of Osteoarthritis- Its Definition, Character, Derivation and Modality-Related Recognition

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Employing molecular genetics of chondrodysplasias to inform the study of osteoarthritis

Cited by 44 publications

References 70 publications

Comprehensive Profiling of Cartilage Extracellular Matrix Formation and Maturation Using Sequential Extraction and Label-free Quantitative Proteomics

Comprehensive Profiling of Cartilage Extracellular Matrix Formation and Maturation Using Sequential Extraction and Label-free Quantitative Proteomics

Avascular necrosis of the femoral head due to a novel C propeptide mutation in COL2A1

Genetic Mouse Models for Osteoarthritis Research

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