title: rhHMGB1 drives osteoblast migration in a TLR2/TLR4- and NF-κB-dependent manner.
abstract: Osteoblast migration is significant in skeletal development. Recently, high mobility group box 1 protein (HMGB1) has been shown to highly expressed in cartilage to regulate endochondral ossification. Nevertheless, whether HMGB1 can modulate osteoblast proliferation and migration is poorly understood, as well as the intracellular signalling pathways that are involved in this process. Herein, we examined the effects of recombinant human HMGB1 (rhHMGB1) on the proliferation and migration of rat osteoblasts and investigated whether Toll-like receptor 2 (TLR2)- and TLR4-dependent signalling pathways are involved in the regulation of intracellular signalling. A transwell chamber assay was used to evaluate the migration of osteoblasts and the MTT assay was used to assess osteoblast proliferation. rhHMGB1 could significantly promote the migration of osteoblasts without inhibiting their proliferation. Meanwhile, rhHMGB1 can increase the nuclear translocation of nuclear factor-kappa B (NF-κB) p65. Specific siRNA constructs that target TLR2 or TLR4 could markedly inhibit HMGB1-induced migration of osteoblasts and HMGB1-enhanced activation of NF-κB. Collectively, HMGB1 could significantly enhance the migration of osteoblasts in vitro, and TLR2/TLR4-dependent NF-κB pathways are involved in HMGB1-induced osteoblast migration.
authors.affiliation: Department of Orthopedic and Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China Department of Pediatric Orthopedic, Wuhan PuAi Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, China.
authors.forename: Ming-Jing
authors.initials: MJ
authors.lastname: Li
authors.affiliation: Department of Pediatric Orthopedic, Wuhan PuAi Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pediatric Orthopedic, Wuhan PuAi Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pediatric Orthopedic, Wuhan PuAi Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, China.
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Liu
authors.affiliation: Department of Pediatric Orthopedic, Wuhan PuAi Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Orthopedic and Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China chenjt2015@tom.com.
authors.forename: Jian-Ting
authors.initials: JT
authors.lastname: Chen
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D024243:HMGB1 Protein / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C498145:Rela protein, rat; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA
keywords: migration; osteoblast; proliferation; recombinant human high mobility group box 1 protein (rhHMGB1); siRNA; skeletal development