{"doi":"10.1677/joe.0.1480355","title":"Transcriptional and post-translational regulation of insulin-like growth factor-binding protein-5 in rat articular chondrocytes","abstract":"<jats:title>Abstract</jats:title>\n        <jats:p>The aim of this study was to assess the regulation of insulin-like growth factor-binding proteins (IGFBPs) by IGFs in primary cultures of rat articular chondrocytes (RAC). Employing Western ligand blotting, immunoprecipitation and Northern blot analysis, RAC were found to secrete IGFBP-5 (29 kDa) and IGFBP-4 (24 kDa) as the predominant IGFBPs, as well as IGFBP-2 (32–30 kDa) and IGFBP-3 (43–39 kDa) as the minor species. Treatment of cells with IGF-I and IGF-II resulted in a dose-dependent increase of IGFBP-5 and a small increase in IGFBP-4 in conditioned media (CM). Des(1–3) IGF-I and [Gln<jats:sup>6</jats:sup>, Ala<jats:sup>7</jats:sup>,Tyr<jats:sup>18</jats:sup>, Leu<jats:sup>19</jats:sup>] IGF-II ([QAYL] IGF-II), which bind to the type 1 IGF receptor but not to IGFBPs, also induced IGFBP-5 peptide, although the increase was less than with IGF-I or IGF-II treatment of RAC. [Leu<jats:sup>27</jats:sup>] IGF-II, which does not bind to the type 1 IGF receptor but binds to IGFBPs, resulted in little induction of IGFBP-5, while [QAYL-Leu<jats:sup>27</jats:sup>] IGF-II, which has reduced affinity for both the type 1 IGF receptor and IGFBPs, did not increase IGFBP-5. These data suggest that the increase in IGFBP-5 in CM is modulated by both the type 1 IGF receptor and the interaction between IGFs and IGFBPs. Northern blotting analysis showed that IGF-I, IGF-II and des(1–3) IGF-I treatment of RAC increased steady state levels of IGFBP-5 mRNA, suggesting that the IGF-mediated increase in IGFBP-5 is transcriptionally modulated. Interestingly, the increase in IGFBP-5 peptide levels and mRNA were not parallel, suggesting the possibility of post-translational modifications of IGFBP-5, such as those seen with IGFBP-5 protease. IGFBP-5 protease activity was detectable in untreated CM, whereas treatment with IGF-I and IGF-II partially protected IGFBP-5 from proteolysis. In summary, treatment of RAC with IGF-I and IGF-II results in dose-dependent increases in both IGFBP-5 peptide in the CM and mRNA levels. These changes are mediated by interactions via the type 1 IGF receptor as well as IGFBPs, both transcriptionally and post-translationally.</jats:p>\n        <jats:p><jats:italic>Journal of Endocrinology</jats:italic> (1996) <jats:bold>148,</jats:bold> 355–369</jats:p>","journal":"Journal of Endocrinology","year":1996,"id":32964,"datarank":1.8362297026941996,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":1.3117535684742274,"self_endowment_contribution":0.5244761342199721,"citer_contribution":1.3117535684742274,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":24,"citers_with_citation_signal":23,"citers_with_endowment":23,"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":173456,"name":"S E Gargosky","orcid":null,"position":1,"is_corresponding":false},{"id":173458,"name":"Y Oh","orcid":null,"position":2,"is_corresponding":false},{"id":118734,"name":"R G Rosenfeld","orcid":null,"position":3,"is_corresponding":false},{"id":173454,"name":"T Matsumoto","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"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":"8699150","pmcid":null,"openalex_id":"https://openalex.org/W2059748240","authors":[],"funders":[{"funder_name":"NICHD NIH HHS","grant_id":"HD 28703","title":null}],"total_grants":1,"fwci":1.7462,"citation_percentile":0.82793624,"influential_citations":2,"citation_trend":[{"year":2022,"count":7},{"year":2024,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://joe.bioscientifica.com/view/journals/joe/148/2/joe_148_2_020.xml","host_type":"publisher"},{"url":"https://joe.bioscientifica.com/downloadpdf/journals/joe/148/2/joe_148_2_020.xml","host_type":"publisher"},{"url":"https://doi.org/10.1677/joe.0.1480355","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8699150","host_type":"repository"}],"fields_of_study":["Growth Hormone and Insulin-like Growth Factors","Metabolism, Diabetes, and Cancer","Cytokine Signaling Pathways and Interactions","Medicine","Biology","Animals","Blotting, Northern","Blotting, Western","Cartilage, Articular","Cells, Cultured","Insulin-Like Growth Factor Binding Protein 5","Male","Precipitin Tests","Protein Biosynthesis","RNA, Messenger","Rats","Rats, Sprague-Dawley","Somatomedins","Transcription, Genetic"],"mesh_terms":["Animals","Cartilage, Articular","Cells, Cultured","Male","Precipitin Tests","RNA, Messenger","Somatomedins","Transcription, Genetic","Protein Biosynthesis","Blotting, Northern","Blotting, Western","Rats, Sprague-Dawley","Insulin-Like Growth Factor Binding Protein 5","Rats"],"keywords":["Internal medicine","Endocrinology","Insulin-like growth factor-binding protein","Insulin-like growth factor","Growth factor","Insulin","Binding protein","Chemistry","Cell biology","Biology","Medicine","Receptor","Biochemistry","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T15:14:12.469855Z","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":[]}