{"doi":"10.1172/jci168447","title":"Bone-derived PDGF-BB drives brain vascular calcification in male mice","abstract":"Brain vascular calcification is a prevalent age-related condition often accompanying neurodegenerative and neuroinflammatory diseases. The pathogenesis of large-vessel calcifications in peripheral tissue is well studied, but microvascular calcification in the brain remains poorly understood. Here, we report that elevated platelet-derived growth factor BB (PDGF-BB) from bone preosteoclasts contributed to cerebrovascular calcification in male mice. Aged male mice had higher serum PDGF-BB levels and a higher incidence of brain calcification compared with young mice, mainly in the thalamus. Transgenic mice with preosteoclast-specific Pdgfb overexpression exhibited elevated serum PDGF-BB levels and recapitulated age-associated thalamic calcification. Conversely, mice with preosteoclast-specific Pdgfb deletion displayed diminished age-associated thalamic calcification. In an ex vivo cerebral microvascular culture system, PDGF-BB dose-dependently promoted vascular calcification. Analysis of osteogenic gene array and single-cell RNA-Seq (scRNA-Seq) revealed that PDGF-BB upregulated multiple osteogenic differentiation genes and the phosphate transporter Slc20a1 in cerebral microvessels. Mechanistically, PDGF-BB stimulated the phosphorylation of its receptor PDGFRβ (p-PDGFRβ) and ERK (p-ERK), leading to the activation of RUNX2. This activation, in turn, induced the transcription of osteoblast differentiation genes in PCs and upregulated Slc20a1 in astrocytes. Thus, bone-derived PDGF-BB induced brain vascular calcification by activating the p-PDGFRβ/p-ERK/RUNX2 signaling cascade in cerebrovascular cells.","journal":"Journal of Clinical Investigation","year":2023,"id":320470,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1019323,"name":"Ching‐Lien Fang","orcid":null,"position":1,"is_corresponding":false},{"id":446906,"name":"Kathleen Noller","orcid":"0000-0001-7915-3269","position":2,"is_corresponding":false},{"id":57473,"name":"Zhiliang Wei","orcid":"0000-0002-8477-2440","position":3,"is_corresponding":false},{"id":242471,"name":"Guanqiao Liu","orcid":"0000-0003-4119-3796","position":4,"is_corresponding":false},{"id":48130,"name":"Ke Shen","orcid":"0000-0003-2818-8124","position":5,"is_corresponding":false},{"id":1031106,"name":"Kangping Song","orcid":"0000-0002-3469-5977","position":6,"is_corresponding":false},{"id":242480,"name":"Xu Cao","orcid":"0000-0001-8614-6059","position":7,"is_corresponding":false},{"id":242481,"name":"Mei Wan","orcid":"0000-0001-9404-540X","position":8,"is_corresponding":false},{"id":863499,"name":"Jiekang Wang","orcid":"0000-0002-1896-9552","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:07:22.377587Z","pmid":"37815871","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":[]}