Fibrocyte enrichment and myofibroblastic adaptation causes nucleus pulposus fibrosis and associates with disc degeneration severity  

作　　者：Yi Sun Yan Peng Zezhuo Su Kyle K.H.So Qiuji Lu Maojiang Lyu Jianwei Zuo Yongcan Huang Zhiping Guan Kenneth M.C.Cheung Zhaomin Zheng Xintao Zhang Victor Y.L.Leung 

机构地区：[1]Department of Sports Medicine,Peking University Shenzhen Hospital,Shenzhen,Guangdong,China [2]Department of Orthopaedics and Traumatology,The University of Hong Kong,Hong Kong SAR,China [3]Department of Spine Surgery,Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies,Peking University Shenzhen Hospital,Shenzhen,Guangdong,China [4]Department of Spine Surgery,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,China

出　　处：《Bone Research》2025年第1期170-182,共13页骨研究(英文版)

基　　金：jointly General Research Fund(17121619)of the Research Grant Council of Hong Kong;Guangdong Basic and Applied Basic Research Foundation(2024A1515010104 and 2023A1515220095);Scientific Research Foundation of Peking University Shenzhen Hospital(KYQD202100X)。

摘　　要：Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic cells in disc degeneration has been reported,yet their nature and origin remain elusive.In this study,we performed an integrative analysis of multiple single-cell RNA sequencing datasets to interrogate the cellular heterogeneity and fibroblast-like entities in degenerative human NP specimens.We found that disc degeneration severity is associated with an enrichment of fibrocyte phenotype,characterized by CD45 and collagen I dual positivity,and expression of myofibroblast markerα-smooth muscle actin.Refined clustering and classification distinguished the fibrocyte-like populations as subtypes in the NP cells-and immunocytes-clusters,expressing disc degeneration markers HTRA1 and ANGPTL4 and genes related to response to TGF-β.In injury-induced mouse disc degeneration model,fibrocytes were found recruited into the NP undergoing fibrosis and adopted a myofibroblast phenotype.Depleting the fibrocytes in CD11b-DTR mice in which myeloid-derived lineages were ablated by diphtheria toxin could markedly attenuate fibrous modeling and myofibroblast formation in the NP of the degenerative discs,and prevent disc height loss and histomorphological abnormalities.Marker analysis supports that disc degeneration progression is dependent on a function of CD45^(+)COL1A1^(+)andαSMA^(+)cells.Our findings reveal that myeloid-derived fibrocytes play a pivotal role in NP fibrosis and may therefore be a target for modifying disc degeneration and promoting its repair.

关 键 词：DEGENERATION SEVERITY markedly 

分 类 号：R74[医药卫生—神经病学与精神病学]