Beyond resorption:osteoclasts as drivers of bone formation  

作　　者：Qianfeng Xiang Lei Li Wei Ji Debby Gawlitta X Frank Walboomers Jeroen J.J.P.van den Beucken 

机构地区：[1]Radboudumc,Dentistry–Regenerative Biomaterials,Philips Van Leijdenlaan 25,Nijmegen 6525EX,the Netherlands [2]State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China [3]Department of Oral and Maxillofacial Surgery&Special Dental Care,University Medical Center Utrecht,Utrecht University,Utrecht,GA 3508,The Netherlands [4]Regenerative Medicine Center Utrecht,Utrecht,CT 3584,The Netherlands [5]Research Institute for Medical Innovation,Radboudumc,Nijmegen,the Netherlands

出　　处：《Cell Regeneration》2024年第1期125-149,共25页细胞再生(英文)

基　　金：China Scholarship Council(File No.202206270002).

摘　　要：Emerging evidence illustrates that osteoclasts(OCs)play diverse roles beyond bone resorption,contributing signifi-cantly to bone formation and regeneration.Despite this,OCs remain mysterious cells,with aspects of their lifespan—from origin,fusion,alterations in cellular characteristics,to functions—remaining incompletely understood.Recent studies have identified that embryonic osteoclastogenesis is primarily driven by osteoclast precursors(OCPs)derived from erythromyeloid progenitors(EMPs).These precursor cells subsequently fuse into OCs essential for normal bone development and repair.Postnatally,hematopoietic stem cells(HSCs)become the primary source of OCs,gradually replacing EMP-derived OCs and assuming functional roles in adulthood.The absence of OCs during bone develop-ment results in bone structure malformation,including abnormal bone marrow cavity formation and shorter long bones.Additionally,OCs are reported to have intimate interactions with blood vessels,influencing bone formation and repair through angiogenesis regulation.Upon biomaterial implantation,activation of the innate immune system ensues immediately.OCs,originating from macrophages,closely interact with the immune system.Furthermore,evi-dence from material-induced bone formation events suggests that OCs are pivotal in these de novo bone formation processes.Nevertheless,achieving a pure OC culture remains challenging,and interpreting OC functions in vivo faces difficulties due to the presence of other multinucleated cells around bone-forming biomaterials.We here describe the fusion characteristics of OCPs and summarize reliable markers and morphological changes in OCs during their fusion process,providing guidance for researchers in identifying OCs both in vitro and in vivo.This review focuses on OC formation,characterization,and the roles of OCs beyond resorption in various bone pathophysiological pro-cesses.Finally,therapeutic strategies targeting OCs are discussed.

关 键 词：OSTEOCLAST Osteoclatogenesis Osteoclast characterization Angiogenesis regulation Bone formation Bone regeneration 

分 类 号：TN9[电子电信—信息与通信工程]