{"doi":"10.1042/bj20030609","title":"Variations in aggrecan structure modulate its susceptibility to aggrecanases","abstract":"<jats:p>Proteoglycan aggregates and purified aggrecan from adult and fetal bovine cartilage and adult and neonatal human cartilage were subjected to in vitro degradation by recombinant aggrecanase-1 and aggrecanase-2. The ability of the aggrecanases to cleave within the aggrecan IGD (interglobular domain) and CS2 domain (chondroitin sulphate-rich domain 2) was monitored by SDS/PAGE and immunoblotting. Aggrecanase-2 showed a similar ability to cleave within the IGD of adult and immature aggrecan, whereas aggrecanase-1 was less efficient in cleavage in the IGD of immature aggrecan, for both the bovine and the human substrates. Both aggrecanases showed a similar ability to cleave within the CS2 domain of bovine aggrecan irrespective of age, but showed a much lower ability to cleave within the CS2 domain of human aggrecan. Equivalent results were obtained whether aggrecan was present in isolation or as part of proteoglycan aggregates. When proteoglycan aggregates were used, neither aggrecanase was able to cleave link protein. Thus, for aggrecan cleavage by aggrecanases, variations in cleavage efficiency exist with respect to the species and age of the animal from which the aggrecan is derived and the type of aggrecanase being used.</jats:p>","journal":"Biochemical Journal","year":2003,"id":627693,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1624666,"name":"James BARNETT","orcid":null,"position":1,"is_corresponding":false},{"id":1624667,"name":"Fengrong ZUO","orcid":null,"position":2,"is_corresponding":false},{"id":1624668,"name":"John S. MORT","orcid":null,"position":3,"is_corresponding":false},{"id":1624665,"name":"Peter J. ROUGHLEY","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Variations in aggrecan structure modulate its susceptibility to aggrecanases","abstract":"<jats:p>Proteoglycan aggregates and purified aggrecan from adult and fetal bovine cartilage and adult and neonatal human cartilage were subjected to in vitro degradation by recombinant aggrecanase-1 and aggrecanase-2. The ability of the aggrecanases to cleave within the aggrecan IGD (interglobular domain) and CS2 domain (chondroitin sulphate-rich domain 2) was monitored by SDS/PAGE and immunoblotting. Aggrecanase-2 showed a similar ability to cleave within the IGD of adult and immature aggrecan, whereas aggrecanase-1 was less efficient in cleavage in the IGD of immature aggrecan, for both the bovine and the human substrates. Both aggrecanases showed a similar ability to cleave within the CS2 domain of bovine aggrecan irrespective of age, but showed a much lower ability to cleave within the CS2 domain of human aggrecan. Equivalent results were obtained whether aggrecan was present in isolation or as part of proteoglycan aggregates. When proteoglycan aggregates were used, neither aggrecanase was able to cleave link protein. Thus, for aggrecan cleavage by aggrecanases, variations in cleavage efficiency exist with respect to the species and age of the animal from which the aggrecan is derived and the type of aggrecanase being used.</jats:p>","is_dataset_classified":null,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12859252","pmcid":"PMC1223671","openalex_id":"https://openalex.org/W1986198423","authors":[],"funders":[],"total_grants":0,"fwci":1.3526,"citation_percentile":0.78012219,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":1},{"year":2014,"count":2},{"year":2015,"count":1},{"year":2016,"count":1},{"year":2018,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://portlandpress.com/biochemj/article-pdf/375/1/183/711504/bj3750183.pdf","host_type":"journal"},{"url":"https://portlandpress.com/biochemj/article-pdf/375/1/183/711504/bj3750183.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1042/bj20030609","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12859252","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1223671","host_type":"repository"}],"fields_of_study":["Proteoglycans and glycosaminoglycans research","RNA Interference and Gene Delivery","Cell Adhesion Molecules Research","ADAM Proteins","ADAMTS4 Protein","ADAMTS5 Protein","Aged","Aggrecans","Animals","Cartilage","Cattle","Extracellular Matrix Proteins","Humans","Infant, Newborn","Lectins, C-Type","Metalloendopeptidases","Procollagen N-Endopeptidase","Protein Structure, Tertiary","Proteoglycans"],"mesh_terms":["ADAMTS5 Protein","ADAMTS4 Protein","Aged","Animals","Cartilage","Cattle","Humans","Infant, Newborn","Metalloendopeptidases","Procollagen N-Endopeptidase","Proteoglycans","Extracellular Matrix Proteins","Protein Structure, Tertiary","Lectins, C-Type","ADAM Proteins","Aggrecans"],"keywords":["Aggrecan","Aggrecanase","Cleave","Chemistry","Proteoglycan","Proteolysis","Cell biology","Biochemistry","Immunoglobulin D","Cartilage","Cleavage (geology)","Biology","Anatomy","Immunology","Enzyme","Extracellular matrix","Osteoarthritis","Medicine","Articular cartilage"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T18:31:31.725805Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}