Role of c-Jun N-terminal kinase in the osteogenic and adipogenic differentiation of human adipose-derived mesenchymal stem cells.
Although previous studies have characterized the osteogenic potential of adipose-derived mesenchymal stem cells (AMSCs) in vitro and in vivo, the molecular mechanism involved remains to be fully determined. Previously, we demonstrated that the ERK pathway plays an important role in osteogenesis and regulation of the balance between osteogenesis and adipogenesis. Here, we explored the possible role of JNKs in osteogenesis and adipogenesis of AMSCs. JNK activation in osteo-induced AMSCs was initiated at 15 min, peaked at 30 min, and declined from 45 min to basal levels. Inhibition of the JNK signaling pathway using SP600125 blocked osteogenic differentiation in a dose-dependent manner, which was revealed by an ALP activity assay, extracellular calcium deposition detection, and expression of osteogenesis-relative genes (Runx2, ALP, and OCN) via RT-PCR and real-time PCR. However, blockage of JNK did not induce a switch between osteogenesis and adipogenesis of AMSCs in the presence of dexamethasone, which is different from that of blockage of ERK. Significantly, the blockage of JNK activation in adipo-induced AMSCs by SP600125 stimulated adipogenic differentiation, which was confirmed by Oil Red O staining to detect intracellular lipid droplets, and RT-PCR and real-time PCR analysis for expression of adipogenesis-relative genes (PPARγ2 and aP2). This study suggested a potential function of the JNK pathway in committing osteogenic and adipogenic differentiation of AMSCs in vitro. However, blockage of the JNK pathway is not sufficient to induce a switch from osteogenesis to adipogenesis of AMSCs.
Department of Orthopedics, Minhang Hospital, Fudan University, 170 Xin Song Road, Shanghai 201199, PR China.
Huijie
H
Gu
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, PR China.
Zhongyue
Z
Huang
Department of Orthopedics, Minhang Hospital, Fudan University, 170 Xin Song Road, Shanghai 201199, PR China.
Xiaofan
X
Yin
Department of Regenerative Medicine, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, PR China.
Jieping
J
Zhang
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, PR China.
Lunli
L
Gong
Department of Orthopedics, Minhang Hospital, Fudan University, 170 Xin Song Road, Shanghai 201199, PR China.
Jiong
J
Chen
Department of Orthopedics, Minhang Hospital, Fudan University, 170 Xin Song Road, Shanghai 201199, PR China.
Ke
K
Rong
Department of Orthopedics, Minhang Hospital, Fudan University, 170 Xin Song Road, Shanghai 201199, PR China.
Jun
J
Xu
Department of Regenerative Medicine, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, PR China; Department of Ophthalmology of the Shanghai Tenth People's Hospital, Tongji Eye Institute, 301 Middle Yan Chang Road, Shanghai 200072, PR China. Electronic address: lulixia@tongji.edu.cn.
Lixia
L
Lu
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, PR China; Medical Technology and Engineering Institute, Henan Science and Technology University, 263 Kaiyuan Road, Luoyang, Henan 471023, PR China. Electronic address: cuileite@aliyun.com.
Lei
L
Cui
D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology* / Q000201:enzymology; D000328:Adult; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D010012:Osteogenesis / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D002118:Calcium
Adipogenesis; Human adipose-derived mesenchymal stem cells; JNK; Osteogenesis