title: Cordycepin protected against the TNF-α-induced inhibition of osteogenic differentiation of human adipose-derived mesenchymal stem cells.
abstract: Cordycepin, 3'-deoxyadenosine, is an effective component isolated from the rare Chinese caterpillar fungus Cordyceps militaris. It exerts potent anti-inflammatory actions in different cell and animal models. However, its action remains unclear on the TNF-α-induced inhibition of osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs). In the present study, we demonstrated that cordycepin induced cell death at 20 and 40 μg/mL. Interestingly, 10 μg/mL cordycepin abrogated the cell death induced by 20 ng/mL TNF-α. Meanwhile, cordycepin exhibited a dose-dependent regulation of the osteogenesis of human ADMSCs: it promoted the differentiation at 10 μg/mL, whereas inhibited differentiation at 40 μg/mL. Furthermore, we discovered that 10 μg/mL cordycepin protected against the TNF-α (induced inhibition of osteogenic differentiation of human ADMSCs. It was also revealed that 10 μg/mL cordycepin restored Runx2 and Osx mRNA levels, which were significantly inhibited by TNF-αduring osteogenesis. At the same time, we found that 10 μg/mL cordycepin suppressed TNF-α-activated NF-κB signaling, by inhibiting IκBα phosphorylation and subsequent p65 release and translocation into the cell nucleus. Of clinical interest, the present study revealed mechanisms involved in inflammatory cytokine-inhibited osteogenesis, and it highlights the potential of cordycepin to promote the osteogenesis of human ADMSCs in cell-based therapy for inflammatory bone diseases.
authors.affiliation: Department of Orthopaedics, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210012, PR China Department of Orthopaedics, Changzhou Traditional Chinese Medical Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, 25 Heping North Road, Changzhou 213000, PR China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University, 29 Xinglong Alley, Changzhou 213003, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Orthopaedics, Changzhou Traditional Chinese Medical Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, 25 Heping North Road, Changzhou 213000, PR China.
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Orthopaedics, Changzhou Traditional Chinese Medical Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, 25 Heping North Road, Changzhou 213000, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210012, PR China.
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Nanjing 211166, PR China uiuciz@126.com lmwang4@163.com.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D050659:Core Binding Factor Alpha 1 Subunit; D003839:Deoxyadenosines; D016328:NF-kappa B; D020011:Protective Agents; D012333:RNA, Messenger; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C058120:cordycepin
keywords: adipose-derived mesenchymal stem cells; bone diseases; cordycepin; inflammation