1.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
2.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
3.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
4.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
5.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
6.Effects of lncRNA MIR22HG on proliferation,apoptosis and inflammatory response of rheumatoid arthritis fibroblast -like synoviocytes by sponge adsorption of miR - 22-5p
Zhou Yang ; Shudian Lin ; Yuwei Zhan ; Lu Xiao ; keying Fu ; Xiaodie Huang
Acta Universitatis Medicinalis Anhui 2023;58(3):405-412
Objective:
To explore the effects of long non-coding RNA (LncRNA) MIR22HG on proliferation,apoptosis and inflammatory response of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and its molecular mechanism.
Methods:
Synovial tissue samples were collected from 37 RA patients and 30 joint trauma patients in our hospital,and the expression levels of MIR22HG and miR-22-5p in synovial tissue were detected by qRT-PCR. RA-FLSs in human was isolated ,cultured and identified in vitro. MIR22HG siRNA interference plasmid (si-MIR22HG) and its negative control plasmid (si-NC) ,miR-22-5p inhibitor and its negative control (inhibitorNC) were transfected into RA-FLSs respectively or simultaneously.The expression levels of MIR22HG and miR- 22-5p were detected by qRT-PCR. CCK-8 was used to detect the proliferation activity of cells in various groups. Annexin Ⅴ- FITC / PI was used to detect the apoptosis rates of cells in various groups.ELISA was used to detect the levels of TNF-α , IL-1 β and IL-6 in the supernatant of cells in various groups.Western blot was used to detect the protein expression levels of Bcl-2,Bax and Cleaved caspase-3 of cells in various groups.The targeting relationship between MIR22HG and miR-22-5p was verified by dual luciferase reporter gene assay.
Results :
Compared with joint trauma patients,the expression level of MIR22HG in synovial tissues of RA patients increased (P<0. 05) , while the expression level of miR-22-5p decreased (P<0. 05) .Interference with MIR22HG inhibited the proliferation activity of RA-FLSs,decreased the levels of TNF-α , IL-1 β and IL-6 in cell supernatant and the protein expression level of Bcl-2 in cells (P<0. 05) ,and increased the apoptosis rate,the expression level of miR-22-5p and the protein expression levels of Bax and Cleaved casepase-3 (P <0. 05 ) .However,inhibition of miR-22-5p expression reversed the effects of MIR22HG gene silencing on proliferation,apoptosis and inflammation of RA-FLSs (P<0. 05) .Dual luciferase reporting assay showed that miR-22-5p was a potential downstream miRNA target of MIR22HG.
Conclusion
MIR22HG is highly expressed in synovial tissues of RA patients,and it may promote the proliferation and the inflammatory response of RA-FLSs and inhibit cell apoptosis by down regulating the expression of miR-22-5p.