1.Effect of stromal cell-derived factor-1 in cartilage and subchondral bone homeostasis
Zhifeng LIANG ; Yingcai YANG ; Qiangang CHENG ; Yongxing JIA ; Bo WANG
Chinese Journal of Tissue Engineering Research 2025;29(25):5422-5433
BACKGROUND:Osteoarthritis is a degenerative disease characterized by cartilage degeneration and abnormal bone remodeling of subchondral bone.In recent years,many studies have shown that stromal cell diffracting factor-1 plays a key role in the pathological progression of osteoarthritis.Targeted regulation of stromal cell-derived factor-1 and its CXC chemokine receptor 4 and CXC chemokine receptor 7 signaling pathways is a new method for prevention and treatment of osteoarthritis.OBJECTIVE:To review the role of stromal derived factor-1 in regulating the proliferation,differentiation,and apoptosis of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,as well as explore the mechanism by which the interaction of these cells leads to cartilage degeneration and abnormal bone remodeling of subchondral bone and accelerates the pathological progression of osteoarthritis,in order to provide new ideas for the prevention and treatment of osteoarthritis.METHODS:CNKI,WanFang Data,and VIP,were searched with Chinese search terms"stromal cell-derived factor 1,cartilage,chondrocytes,subchondral bone,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,CXC chemokine receptor 4,CXC chemokine receptor 7."PubMed,Medline,and Embase databases were searched with English search terms"stromal cell-derived factor 1,SDF-1,CXCL12,cartilage,chondrocyte,subchondral bone,mesenchymal stem cells,osteoblasts,osteoclasts,CXCR4,CXCR7."Literature retrieval time was from inception to January 2024.A total of 77 articles were included and summarized in accordance with the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Stromal cell-derived factor-1 regulates the migration,proliferation,differentiation,and death of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,which plays an important role in maintaining cartilage and subchondral bone homeostasis,promoting or inhibiting cartilage degeneration and abnormal bone remodeling in osteoarthritis.Targeted regulation of stromal cell-derived factor-1/CXC chemokine receptor type 4/CXC chemokine receptor type 7 signaling pathway is expected to become the focus of future research on the prevention and treatment of osteoarthritis.(2)Because of the difference in the expression of stromal cell-derived factor-1 subtypes in tissues,stromal cell-derived factor-1 α is the most widely studied at present.The related studies of stromal cell-derived factor-1β and stromal cell-derived factor-1y are mainly focused on exploring the effects on the biological behavior of stem cells,the role in the regulation of cartilage and subchondral bone homeostasis,and the correlation with osteoarthritis.(3)Stromal cell-derived factor-1 can effectively promote stem cells homing to cartilage injury sites,and induce their proliferation,survival,and cartilage differentiation.The application of stromal cell-derived factor-1-loaded biological scaffolds to improve the quality of cartilage repair has become the focus of cartilage tissue engineering research.However,previous studies have shown that stromal cell-derived factor-1 can promote the differentiation of bone marrow mesenchymal stem cells into hypertrophic chondrocytes,while the hypertrophic phenotype of newborn chondrocytes can lead to endochondral bone formation and chondrocyte apoptosis.The whole tissue is vascularized and ossified,which affects the quality of cartilage repair.In addition,when different scaffolds combined with stromal cell-derived factor-1 can repair partial cartilage injury and full-thickness cartilage injury,the regenerated tissue is not all ideal hyaline cartilage tissue.Therefore,in the future,in-depth exploration of the potential mechanism of stromal cell-derived factor-1 in stem cell biological effects and the best combination of stromal cell-derived factor-1 and scaffold in repairing different cartilage defects will help to improve the quality of cartilage repair.(4)The studies on CXC chemokine receptor 4 antagonists are mainly focused on AMD3100,T140 and TN14003,and most of them are in the basic experimental stage and need to be transformed into clinical practice.The safety and effectiveness of the therapeutic drugs developed for stromal cell-derived factor-1/CXC chemokine receptor 4/CXC chemokine receptor 7 signaling pathway still need a large number of biological and clinical trials to support.
2.Effect of stromal cell-derived factor-1 in cartilage and subchondral bone homeostasis
Zhifeng LIANG ; Yingcai YANG ; Qiangang CHENG ; Yongxing JIA ; Bo WANG
Chinese Journal of Tissue Engineering Research 2025;29(25):5422-5433
BACKGROUND:Osteoarthritis is a degenerative disease characterized by cartilage degeneration and abnormal bone remodeling of subchondral bone.In recent years,many studies have shown that stromal cell diffracting factor-1 plays a key role in the pathological progression of osteoarthritis.Targeted regulation of stromal cell-derived factor-1 and its CXC chemokine receptor 4 and CXC chemokine receptor 7 signaling pathways is a new method for prevention and treatment of osteoarthritis.OBJECTIVE:To review the role of stromal derived factor-1 in regulating the proliferation,differentiation,and apoptosis of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,as well as explore the mechanism by which the interaction of these cells leads to cartilage degeneration and abnormal bone remodeling of subchondral bone and accelerates the pathological progression of osteoarthritis,in order to provide new ideas for the prevention and treatment of osteoarthritis.METHODS:CNKI,WanFang Data,and VIP,were searched with Chinese search terms"stromal cell-derived factor 1,cartilage,chondrocytes,subchondral bone,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,CXC chemokine receptor 4,CXC chemokine receptor 7."PubMed,Medline,and Embase databases were searched with English search terms"stromal cell-derived factor 1,SDF-1,CXCL12,cartilage,chondrocyte,subchondral bone,mesenchymal stem cells,osteoblasts,osteoclasts,CXCR4,CXCR7."Literature retrieval time was from inception to January 2024.A total of 77 articles were included and summarized in accordance with the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Stromal cell-derived factor-1 regulates the migration,proliferation,differentiation,and death of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,which plays an important role in maintaining cartilage and subchondral bone homeostasis,promoting or inhibiting cartilage degeneration and abnormal bone remodeling in osteoarthritis.Targeted regulation of stromal cell-derived factor-1/CXC chemokine receptor type 4/CXC chemokine receptor type 7 signaling pathway is expected to become the focus of future research on the prevention and treatment of osteoarthritis.(2)Because of the difference in the expression of stromal cell-derived factor-1 subtypes in tissues,stromal cell-derived factor-1 α is the most widely studied at present.The related studies of stromal cell-derived factor-1β and stromal cell-derived factor-1y are mainly focused on exploring the effects on the biological behavior of stem cells,the role in the regulation of cartilage and subchondral bone homeostasis,and the correlation with osteoarthritis.(3)Stromal cell-derived factor-1 can effectively promote stem cells homing to cartilage injury sites,and induce their proliferation,survival,and cartilage differentiation.The application of stromal cell-derived factor-1-loaded biological scaffolds to improve the quality of cartilage repair has become the focus of cartilage tissue engineering research.However,previous studies have shown that stromal cell-derived factor-1 can promote the differentiation of bone marrow mesenchymal stem cells into hypertrophic chondrocytes,while the hypertrophic phenotype of newborn chondrocytes can lead to endochondral bone formation and chondrocyte apoptosis.The whole tissue is vascularized and ossified,which affects the quality of cartilage repair.In addition,when different scaffolds combined with stromal cell-derived factor-1 can repair partial cartilage injury and full-thickness cartilage injury,the regenerated tissue is not all ideal hyaline cartilage tissue.Therefore,in the future,in-depth exploration of the potential mechanism of stromal cell-derived factor-1 in stem cell biological effects and the best combination of stromal cell-derived factor-1 and scaffold in repairing different cartilage defects will help to improve the quality of cartilage repair.(4)The studies on CXC chemokine receptor 4 antagonists are mainly focused on AMD3100,T140 and TN14003,and most of them are in the basic experimental stage and need to be transformed into clinical practice.The safety and effectiveness of the therapeutic drugs developed for stromal cell-derived factor-1/CXC chemokine receptor 4/CXC chemokine receptor 7 signaling pathway still need a large number of biological and clinical trials to support.
3.Clinical and histologic improvements in patients with hepatitis B virus-related compensated cirrhosis ;after long-term antiviral treatment
Lingjun YING ; Huazhong CHEN ; Jianwei ZHANG ; Hui SHAO ; Qiangang CHENG ; Junyan LIU ; Yongzhi TANG ; Weiti WU
Chinese Journal of Clinical Infectious Diseases 2016;(1):13-18
Objective To investigate the effect of long-term antiviral treatment on clinical outcome and liver histology in patients with hepatitis B virus ( HBV)-related compensated cirrhosis .Methods A total of 61 patients with HBV-related compensated cirrhosis receiving antiviral therapy were enrolled from Taizhou Hospital of Zhejiang Province during September 2010 and March 2015, including 26 HBeAg-positive cases and 35 HBeAg-negative cases .Thirty-nine patients were treated with entecavir ( ETV ) and 22 were treated with adefovir dipivoxil ( ADV ) .Biochemical , serological and virological markers were examined every 3 months during treatment, and Child-Turcotte-Pugh (CTP) scores were calculated.All the patients underwent liver biopsy before and 144 weeks after antiviral treatment .Metavir scoring system was used to evaluate the liver histological activity ( A) and fibrosis score ( F) .Wilcoxon rank sum test and paired t-test were used for the evaluation of liver histopathology and liver function before and after treatment , respectively.Results After 144 weeks of antiviral treatment , HBV DNA was reduced and below the lower limit of detection in 58 patients (95.1%), HBeAg disappeared in 14 patients (14/26, 53.8%), and HBeAg seroconversion was observed in 10 patients (10/26, 38.5%); alanine aminotransferase ( ALT), aspartate amino transaminase (AST), total bilirubin (TBil) and CTP score decreased (t=7.489, 8.259, 14.000 and 6.026, all P<0.01), prothrombin time (PT) was shortened (t=9.777, P<0.01), and serum albumin (Alb) increased (t=3.446, P<0.01).Improvements in both liver histologic activity and fibrosis score were observed (Z=5.716 and 6.657, all P<0.01).Liver histological activity decreased from A1 to A0 in 16 cases, from A2 to A0 in 9 cases, from A2 to A1 in 15 cases, from A3 to A0 in 1 case, from A3 to A1 in 5 cases, and from A3 to A2 in 5 cases.Fibrosis score at the baseline was F 4 for all patients, while after treatment, there were 7 patients with F1, 22 with F2, 20 with F3, and F4 remained in rest 12 patients.Conclusion Both clinical and histological improvements can be obtained after long-term antiviral treatment for patients with HBV-related compensated cirrhosis .

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