In Vivo Identification and Induction of Articular Cartilage Stem Cells by Inhibiting NF-κB Signaling in Osteoarthritis.
Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder characterized by the degeneration of articular cartilage. However, no effective medical therapy has been found yet for such condition. In this study, we directly confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, and explored their chondrogenesis in Interleukin-1β (IL-1β) induced inflammation environment and disclose whether the inhibition of NF-κB signaling can induce ACSCs activation thus improve the progression of experimental OA. We found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair. During the in vitro mechanism study, we discovered IL-1β can efficiently activate the NF-κB pathway and potently impair the responsiveness of ACSCs, whereas the NF-κB pathway inhibitor rescued the ACSCs chondrogenesis. The final in vivo experiments further confirmed ACSCs' activation were maintained by NF-κB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model. Our results provided in vivo evidence of the presence of ACSCs, and disclosed their action in the early OA stage and gradual quiet as OA process, presented a potential mechanism for both cartilage intrinsic repair and its final degradation, and demonstrated the feasibility of inducing endogenous adult tissue-specific mesenchymal stem cells for articular cartilage repair and OA therapy.
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.|Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.
Wenxue
W
Tong
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.
Yiyun
Y
Geng
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.|Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Yan
Y
Huang
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.
Yu
Y
Shi
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.
Shengnan
S
Xiang
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.
Ning
N
Zhang
Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.
Ling
L
Qin
Orthopaedics Research Laboratory, Research Center, Sacré-Coeur Hospital, University of Montreal, Montreal, Quebec, Canada.
Qin
Q
Shi
Cell and Molecular Biology Laboratory, Department of Orthopaedics, Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA.
Qian
Q
Chen
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.|Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Kerong
K
Dai
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.|Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Xiaoling
X
Zhang
D000818:Animals; D002358:Cartilage, Articular / Q000254:growth & development / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics
D053583:Interleukin-1beta; D016328:NF-kappa B
Articular cartilage stem cells; Identification; Induction; NF-κB signaling; Osteoarthritis