{"doi":"10.1172/jci147116","title":"Skeleton-secreted PDGF-BB mediates arterial stiffening","abstract":"Evidence links osteoporosis and cardiovascular disease but the cellular and molecular mechanisms are unclear. Here we identify skeleton-secreted platelet-derived growth factor-BB (PDGF-BB) as a key mediator of arterial stiffening in response to aging and metabolic stress. Aged mice and those fed high-fat diet (HFD), relative to young mice and those fed normal chow food diet, respectively, had higher serum PDGF-BB and developed bone loss and arterial stiffening. Bone/bone marrow preosteoclasts in aged mice and HFD mice secrete an excessive amount of PDGF-BB, contributing to the elevated PDGF-BB in blood circulation. Conditioned medium prepared from preosteoclasts stimulated proliferation and migration of the vascular smooth muscle cells. Conditional transgenic mice, in which PDGF-BB is overexpressed in preosteoclasts, had 3-fold higher serum PDGF-BB concentration and developed simultaneous bone loss and arterial stiffening spontaneously at a young age. Conversely, in conditional knockout mice, in which PDGF-BB is deleted selectively in preosteoclasts, HFD did not affect serum PDGF-BB concentration; as a result, HFD-induced bone loss and arterial stiffening were attenuated. These studies confirm that preosteoclasts are a main source of excessive PDGF-BB in blood circulation during aging and metabolic stress and establish the role of skeleton-derived PDGF-BB as an important mediator of vascular stiffening.","journal":"Journal of Clinical Investigation","year":2021,"id":157493,"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":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":242471,"name":"Guanqiao Liu","orcid":"0000-0003-4119-3796","position":1,"is_corresponding":false},{"id":664594,"name":"Sandeep Jandu","orcid":"0000-0002-3931-9372","position":2,"is_corresponding":false},{"id":242470,"name":"Weiping Su","orcid":"0000-0002-6261-8661","position":3,"is_corresponding":false},{"id":665502,"name":"Bulouere P. Wodu","orcid":null,"position":4,"is_corresponding":false},{"id":665503,"name":"William Savage","orcid":null,"position":5,"is_corresponding":false},{"id":665504,"name":"Alan Poe","orcid":null,"position":6,"is_corresponding":false},{"id":242472,"name":"Xiaonan Liu","orcid":"0000-0003-3661-7961","position":7,"is_corresponding":false},{"id":339385,"name":"Lacy M. Alexander","orcid":"0000-0002-1294-8582","position":8,"is_corresponding":false},{"id":312076,"name":"Xu Cao","orcid":"0000-0002-8749-1716","position":9,"is_corresponding":false},{"id":242481,"name":"Mei Wan","orcid":"0000-0001-9404-540X","position":10,"is_corresponding":false},{"id":665501,"name":"Lakshmi Santhanam","orcid":null,"position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-18T23:44:21.786014Z","pmid":"34437300","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":[]}