Osteoblast derived-neurotrophin‑3 induces cartilage removal proteases and osteoclast-mediated function at injured growth plate in rats
| Autor: | Di Chen, Yuwen Su, Xin-Fu Zhou, Lin Chen, Yangli Xie, Clive A. Prestidge, Rosa Chung, Jiake Xu, Lisa M. Butler, Shek Man Chim, Lin Zhou, Stan Gronthos, Cory J. Xian, Yaser Peymanfar, Mohammadhossein Hassanshahi, Chiaming Fan, Bruce K. Foster, Yunmei Song, Qian Tang |
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| Přispěvatelé: | Su, Yu Wen, Chim, Shek Man, Zhou, Lin, Hassanshahi, Mohammadhossein, Chung, Rosa, Fan, Chiaming, Song, Yunmei, Foster, Bruce K., Prestidge, Clive A., Peymanfar, Yaser, Tang, Qian, Butler, Lisa M., Gronthos, Stan, Chen, Di, Xie, Yangli, Chen, Lin, Zhou, Xin Fu, Xu, Jiake, Xian, Cory J. |
| Rok vydání: | 2018 |
| Předmět: |
Cartilage
Articular Male musculoskeletal diseases 0301 basic medicine Proteases Histology Stromal cell neurotrophic factors growth plate injury Physiology Endocrinology Diabetes and Metabolism Osteoclasts signal crosstalk Article Rats Sprague-Dawley Mice 03 medical and health sciences Neurotrophin 3 Osteogenesis Osteoclast medicine Animals Humans Receptor trkC Growth Plate RNA Messenger Bony Callus Cathepsin Bone growth Osteoblasts NFATC Transcription Factors biology Chemistry Cartilage RANK Ligand NF-kappa B Osteoblast injury site remodelling Cell biology Enzyme Activation RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure RANKL biology.protein Cytokines Peptide Hydrolases |
| Zdroj: | Bone. 116:232-247 |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/j.bone.2018.08.010 |
| Popis: | Faulty bony repair causes dysrepair of injured growth plate cartilage and bone growth defects in children; however, the underlying mechanisms are unclear. Recently, we observed the prominent induction of neurotrophin‑3 (NT-3) and its important roles as an osteogenic and angiogenic factor promoting the bony repair. The current study investigated its roles in regulating injury site remodelling. In a rat tibial growth plate drill-hole injury repair model, NT-3 was expressed prominently in osteoblasts at the injury site. Recombinant NT-3 (rhNT-3) systemic treatment enhanced, but NT-3 immunoneutralization attenuated, expression of cartilage-removal proteases (MMP-9 and MMP-13), presence of bone-resorbing osteoclasts and expression of osteoclast protease cathepsin K, and remodelling at the injury site. NT-3 was also highly induced in cultured mineralizing rat bone marrow stromal cells, and the conditioned medium augmented osteoclast formation and resorptive activity, an ability that was blocked by presence of anti-NT-3 antibody. Moreover, NT-3 and receptor TrkC were induced during osteoclastogenesis, and rhNT-3 treatment activated TrkC downstream kinase Erk1/2 in differentiating osteoclasts although rhNT-3 alone did not affect activation of osteoclastogenic transcription factors NF-κB or NFAT in RAW264.7 osteoclast precursor cells. Furthermore, rhNT-3 treatment increased, but NT-3 neutralization reduced, expression of osteoclastogenic cytokines (RANKL, TNF-α and IL-1) in mineralizing osteoblasts and in growth plate injury site, and rhNT-3 augmented the induction of these cytokines caused by RANKL treatment in RAW264.7 cells. Thus, injury site osteoblast-derived NT-3 is important in promoting growth plate injury site remodelling, as it induces cartilage proteases for cartilage removal and augments osteoclastogenesis and resorption both directly (involving activing Erk1/2 and substantiating RANKL-induced increased expression of osteoclastogenic signals in differentiating osteoclasts) and indirectly (inducing osteoclastogenic signals in osteoblasts). Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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