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However, little is known about altered synovial cellular compositions, their associated transcriptomic profiles, and cell\u2013cell interactions in FAI and hip OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Synovial samples from a sex\u2010matched cohort of patients with FAI and hip OA (n\u00a0=\u00a06 per condition) were analyzed using integrative single\u2010cell RNA sequencing and spatial transcriptomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to FAI, epiregulin (EREG)\u2010enriched lining synovial fibroblast\u2010like synoviocytes (FLS) were significantly increased in hip OA.\n                      <jats:italic>EREG<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      FLS are proinflammatory due to elevated expression of\n                      <jats:italic>CXCL1<\/jats:italic>\n                      ,\n                      <jats:italic>IL8<\/jats:italic>\n                      , and\n                      <jats:italic>MMPs<\/jats:italic>\n                      . Pseudotime analysis predicts that\n                      <jats:italic>EREG<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      FLS are derived from\n                      <jats:italic>DPP4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>PI16<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      sublining FLS, likely regulated by NFIX and REL, as well as ELK3 and ETV6 transcription factors under FAI or OA conditions, respectively. Importantly, the only putative cell\u2013cell interaction is fibroblast growth factor 2 (FGF2)\u2013syndecan 4 (SDC4) communication between\n                      <jats:italic>COL1A1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>IGFBP5<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      fibrotic macrophages and\n                      <jats:italic>EREG<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      FLS. This interaction may induce expression of interleukin (IL)\u20106, IL\u20108, and matrix metalloproteinase 1 (MMP1) in hip OA synovium. The Gene Ontology analysis of activated genes downstream of FGF2\u2010SDC4 signaling revealed that inflammation and angiogenesis were up\u2010regulated in hip OA, whereas positive gene transcription and skeletal muscle differentiation were dominant in FAI. Moreover, we also found that\n                      <jats:italic>EREG<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>CCL20<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>MMP3<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>hi<\/jats:italic>\n                      <\/jats:sup>\n                      lining FLS along with most macrophage and monocyte populations are unique to patients with hip OA compared to patients with knee OA and rheumatoid arthritis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings of this study offer a groundwork in tailoring novel targets and therapies for patients with FAI and hip OA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70033","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T14:28:02Z","timestamp":1768228082000},"page":"1219-1230","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrative Single\u2010Cell\n                    <scp>RNA<\/scp>\n                    Sequencing and Spatial Transcriptomics Uncover Distinct Fibroblast\u2013Macrophage Crosstalk in Human Hip Synovium Between Patients With Femoroacetabular Impingement and Osteoarthritis"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3946-1275","authenticated-orcid":false,"given":"Gulzada","family":"Kulzhanova","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery and Rehabilitation, Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New York"},{"name":"Department of Biomedical Engineering University of Rochester  Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Klee","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Rehabilitation, Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Botros","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Rehabilitation, Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Rehabilitation, Center for Musculoskeletal Research University of Rochester Medical Center  Rochester New 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