1.Is unicompartmental knee arthroplasty a better choice than total knee arthroplasty for unicompartmental osteoarthritis? A systematic review and meta-analysis of randomized controlled trials.
Kuanyu XIA ; Lang MIN ; Wenqing XIE ; Guang YANG ; Dong Keon YON ; Seung Won LEE ; Ai KOYANAGI ; Louis JACOB ; Lee SMITH ; Jae Il SHIN ; Masoud RAHMATI ; Wenfeng XIAO ; Yusheng LI
Chinese Medical Journal 2025;138(13):1568-1577
BACKGROUND:
The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA.
METHODS:
PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards.
RESULTS:
Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction.
CONCLUSIONS
In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans
;
Arthroplasty, Replacement, Knee/methods*
;
Osteoarthritis, Knee/surgery*
;
Randomized Controlled Trials as Topic
;
Treatment Outcome
2.Key roles of the superficial zone in articular cartilage physiology, pathology, and regeneration.
Li GUO ; Pengcui LI ; Xueqin RONG ; Xiaochun WEI
Chinese Medical Journal 2025;138(12):1399-1410
The superficial zone (SFZ) of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimuli. The SFZ is not only a crucial structure for maintaining the normal physiological function of articular cartilage but also the earliest site of osteoarthritis (OA) cartilage degeneration and a major site of cartilage progenitor cells, suggesting that the SFZ might represent a key target for the early diagnosis and treatment of OA. However, to date, SFZ research has not received sufficient attention, accounting for only about 0.58% of cartilage tissue research. The structure, biological composition, function, and related mechanisms of the SFZ in the physiological and pathological processes of articular cartilage remain unclear. This article reviews the key role of the SFZ in articular cartilage physiology and pathology and focuses on the characteristics of SFZ in articular cartilage degeneration and regeneration in OA, aiming to provide researchers with a systematic understanding of the current research status of the SFZ of articular cartilage, hoping that scholars will give more attention to the SFZ of articular cartilage in the future.
Cartilage, Articular/pathology*
;
Humans
;
Regeneration/physiology*
;
Animals
;
Osteoarthritis/physiopathology*
3.Correlation between severity of knee joint osteoarthritis and alignment of patellofemoral and patellar height on radiographs.
Zhenlei YANG ; Mingjie SHEN ; Deshun XIE ; Junzhe ZHANG ; Qingjun WEI
Chinese Medical Journal 2025;138(8):947-952
BACKGROUND:
The correlation between the morphological structure of the patellofemoral joint (PFJ) and the severity of knee joint osteoarthritis (KOA) remains uncertain. This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs.
METHODS:
This multi-center, retrospective study analyzed the magnetic resonance imaging (MRI) scans and anteroposterior radiographs of 534 adult outpatients with KOA. To evaluate the radiographic severity of KOA, anteroposterior radiographs of the knee and the Kellgren-Lawrence (K-L) grade were used. Knee MRI scans were used to measure the patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt angle (LPTA), and the distance between tibial tuberosity and trochlear groove (TT-TG). We examined the association between the configuration of the PFJ, arrangement, and harshness of the KOA. Information on participants' demographics, such as age, sex, side, height, and weight, was collected. A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side. Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA. Multiple linear regression models were used for the association between LPTA, SA, TT-TG, and severity of KOA after accounting for demographic variables.
RESULTS:
The study comprised of 534 patients; of these, 339 (63%) were female. A total of 586 knees were evaluated in this study. Age showed a strong positive correlation with KOA severity ( r = 0.516, P <0.01), whereas LPTA showed a strong negative correlation ( r = -0.662, P <0.01). Additionally, SA ( r = 0.616, P <0.05), and TT-TG showed a strong positive correlation ( r = 0.770, P <0.01) with tibiofemoral osteoarthritis (TFOA) severity. Multiple linear regression analysis indicated that knee osteoarthritis severity (β = -2.946, P <0.001) and side (β = -0.839, P = 0.001) was associated with LPTA; knee osteoarthritis severity (β = 5.032, P <0.001) and age (β = -0.095, P <0.001) was associated with SA; knee osteoarthritis severity (β = 2.445, P <0.001), sex (β = -0.326, P = 0.041), body mass index (β = -0.061, P = 0.017) and age (β = -0.025, P <0.001) was associated with TT-TG.
CONCLUSION
Radiographic severity of KOA was positively associated with age, SA, and TT-TG but negatively associated with LPTA.
Humans
;
Female
;
Male
;
Osteoarthritis, Knee/pathology*
;
Middle Aged
;
Retrospective Studies
;
Aged
;
Patellofemoral Joint/pathology*
;
Magnetic Resonance Imaging
;
Adult
;
Patella/pathology*
;
Radiography
4.EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis by regulating endoplasmic reticulum stress in knee osteoarthritis.
Yang CHEN ; Shanshan DONG ; Xin ZENG ; Qing XU ; Mingwei LIANG ; Guangneng LIAO ; Lan LI ; Bin SHEN ; Yanrong LU ; Haibo SI
Chinese Medical Journal 2025;138(1):79-92
BACKGROUND:
Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported.
METHODS:
The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats.
RESULTS:
Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis.
CONCLUSIONS
A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics*
;
Osteoarthritis, Knee/pathology*
;
Chondrocytes/metabolism*
;
Pyroptosis/physiology*
;
HMGB1 Protein/genetics*
;
MicroRNAs/metabolism*
;
Endoplasmic Reticulum Stress/genetics*
;
Humans
;
Animals
;
Rats
;
Male
;
Rats, Sprague-Dawley
;
Middle Aged
5.Kaempferide inhibited progression of osteoarthritis by targeting the HIF-1 signaling pathway.
Xianjie WEI ; Hesuyuan HUANG ; Ping YUAN ; Peisen XIE ; Keshi ZHANG ; Zhenpeng GUAN
Chinese Medical Journal 2025;138(21):2813-2823
BACKGROUND:
Osteoarthritis (OA) is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability. As the global burden of OA continues to rise, novel therapeutic strategies are urgently needed. Kaempferide (KA), a flavonoid derived from traditional Chinese herbal medicine, is known for its anti-inflammatory properties. However, the effect of KA on the progression of OA has not been well investigated. This study aimed to explore the therapeutic potential of KA in an OA model and investigate the underlying mechanisms via transcriptomic sequencing.
METHODS:
An in vitro OA model was established using SW1353 cells treated with interleukin-1 beta (IL-1β) and different concentrations of KA (30, 60, or 90 μmol/L) for 24 h. The anti-inflammatory effects of KA were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting. In vivo , a papain-induced OA rat model was used to evaluate the therapeutic effects of KA through histological and behavioral analyses. Transcriptomic sequencing was performed to explore the differentially expressed genes (DEGs) and related signaling pathways. Statistical analysis was conducted using one-way analysis of variance.
RESULTS:
KA significantly increased cell viability in the OA chondrocyte model and downregulated the expression of inflammatory cytokines and cartilage degradation markers, with the greatest reduction observed at 90 μmol/L. In vivo , KA treatment mitigated cartilage degradation and improved gait behavior in OA rats. Transcriptomic analysis revealed substantial modulation of DEGs, implicating the hypoxia-inducible factor-1 (HIF-1) signaling pathway as a key mechanism. Further blocking and rescue experiments revealed that KA regulated key molecules within the HIF-1 pathway, specifically interferon-gamma (IFN-γ) and hypoxia-inducible factor 1-alpha (HIF-1α), confirming their critical roles in mediating the therapeutic effects of KA.
CONCLUSION
KA inhibited the progression of OA by targeting the HIF-1 signaling pathway, reducing inflammation, and cartilage degradation.
Animals
;
Osteoarthritis/metabolism*
;
Signal Transduction/drug effects*
;
Rats
;
Rats, Sprague-Dawley
;
Humans
;
Male
;
Hypoxia-Inducible Factor 1/metabolism*
;
Interleukin-1beta
6.Effect of Duhuo Jisheng Decoction on knee osteoarthritis model rabbits through regulation of cell pyroptosis mediated by PI3K/Akt/mTOR signaling pathway.
Lin-Qin HE ; Peng-Fei LI ; Xiao-Dong LI ; Qi-Peng CHEN ; Zong-Han TANG ; Yu-Xin SONG ; Han-Bing SONG
China Journal of Chinese Materia Medica 2025;50(1):187-197
This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Rabbits
;
TOR Serine-Threonine Kinases/genetics*
;
Osteoarthritis, Knee/genetics*
;
Proto-Oncogene Proteins c-akt/genetics*
;
Signal Transduction/drug effects*
;
Male
;
Disease Models, Animal
;
Pyroptosis/drug effects*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Humans
;
Female
7.Characterization of protective effects of Jianpi Tongluo Formula on cartilage in knee osteoarthritis from a single cell-spatial heterogeneity perspective.
Yu-Dong LIU ; Teng-Teng XU ; Zhao-Chen MA ; Chun-Fang LIU ; Wei-Heng CHEN ; Na LIN ; Yan-Qiong ZHANG
China Journal of Chinese Materia Medica 2025;50(3):741-749
This study aims to integrate data mining techniques of single cell transcriptomics and spatial transcriptomics, along with animal experiment validation, so as to systematically characterize the protective effects of Jianpi Tongluo Formula(JTF) on the cartilage in knee osteoarthritis(KOA) and elucidate the underlying molecular mechanisms. Single cell transcriptomics and spatial transcriptomics datasets(GSE254844 and GSE255460) of the cartilage tissue obtained from KOA patients were analyzed to map the single cell-spatial heterogeneity and identify key pathogenic factors. After that, a KOA rat model was established via knee joint injection of papain. The intervention effects of JTF on the expression features of these key factors were assessed through real-time quantitative polymerase chain reaction(PCR), Western blot, and immunohistochemical staining. As a result, the integrated single cell and spatial transcriptomics data identified distinct cell subsets with different pathological changes in different regions of the inflamed cartilage tissue in KOA, and their differentiation trajectories were closely related to the inflammatory fibrosis-like pathological changes of chondrocytes. Accordingly, the expression levels of the two key effect targets, namely nuclear receptor coactivator 4(NCOA4) and high mobility group box 1(HMGB1) were significantly reduced in the articular surface and superficial zone of the inflamed joints when JTF effectively alleviated various pathological changes in KOA rats, thus reversing the abnormal chondrocyte autophagy level, relieving the inflammatory responses and fibrosis-like pathological changes, and promoting the repair of chondrocyte function. Collectively, this study revealed the heterogeneous characteristics and dynamic changes of inflamed cartilage tissue in different regions and different cell subsets in KOA patients. It is worth noting that NCOA4 and HMGB1 were crucial in regulating chondrocyte autophagy and inflammatory reaction, while JTF could reverse the regulation of NCOA4 and HMGB1 and correct the abnormal molecular signal axis in the target cells of the inflamed joints. The research can provide a new research idea and scientific basis for developing a personalized therapeutic schedule targeting the spatiotemporal heterogeneity characteristics of KOA.
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Rats
;
Osteoarthritis, Knee/pathology*
;
Humans
;
Male
;
Cartilage, Articular/metabolism*
;
Chondrocytes/metabolism*
;
Rats, Sprague-Dawley
;
Female
;
Protective Agents/administration & dosage*
;
Single-Cell Analysis
;
Middle Aged
;
HMGB1 Protein/metabolism*
8.Characterization and features of dampness-heat obstruction syndrome in rats with knee osteoarthritis based on "disease-syndrome-symptom" combination research strategy.
Li-Li WANG ; Teng-Teng XU ; Xiao-Xiao WANG ; Qun LI ; Li-Ting XU ; Wei-Heng CHEN ; Chun-Fang LIU ; Na LIN
China Journal of Chinese Materia Medica 2025;50(7):1861-1871
A combination of the "disease-syndrome-symptom" approach was used to study the syndrome characterization and features of dampness-heat obstruction syndrome in papain-induced knee osteoarthritis(KOA) model rats during the disease process. Forty-eight male SD rats were randomly divided into sham and model groups. The KOA model was established by injecting a mixture of papain and L-cysteine into the joint cavity on days 1, 3, and 5. During the 8 weeks following model establishment, the rats were assessed weekly for the plantar mechanical pain threshold, knee joint diameter, local skin temperature of the knee joint, weight-bearing difference between the two hind feet, and the modified Lequesne MG score of the knee joint. Samples were collected at 1, 2, 4, 6, and 8 weeks after model establishment to observe the gross lesions in cartilage and synovium. Histopathological changes in joint tissues were examined using hematoxylin-eosin, Masson's trichrome, and Senna red O-solid green staining. ELISA and immunohistochemical analysis were performed to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, prostaglandin E2(PGE2), and the expression of aquaporins(AQP) 1 and 3 in serum and synovium. The results showed that the ink score of articular cartilage in the model group significantly increased from 4 to 8 weeks, the cartilage Mankin's score and the percentage of Masson-positive area in cartilage increased significantly from 1 to 8 weeks. The percentage of red-stained area for cartilage proteoglycans decreased significantly from 1 to 8 weeks. The synovitis score from 1 to 6 weeks and the percentage of blue-stained collagen fibers in the synovium from 1 to 8 weeks increased significantly, with statistically significant differences compared to the sham group. The mechanical pain threshold in the model group significantly decreased from 1 to 8 weeks, the knee joint diameter significantly increased from 1 to 6 weeks, and the local skin temperature of the knee joint, the weight-bearing difference between the two hind feet, and the modified Lequesne MG score from 1 to 5 weeks significantly increased, all with statistically significant differences compared to the sham group. The levels of IL-1β, IL-6, TNF-α, and PGE2 in serum and synovium of the model group significantly increased from 1 to 6 weeks. Serum TNF-α and PGE2, and synovial IL-1β, also significantly increased at 8 weeks. The levels of cartilage AQP1 and AQP3 significantly increased from 1 to 4 weeks, while synovial AQP1 and AQP3 increased significantly from 1 to 6 weeks, with all differences statistically significant compared to the sham group. In conclusion, papain-induced KOA rats exhibited pathological changes, including articular cartilage degeneration and synovial inflammation, within 1 week of induction. The KOA rats showed characteristics of dampness-heat obstruction syndrome, such as joint pain, swelling, elevated skin temperature, and decreased function, as well as increased inflammatory factors and AQP1、AQP3 in serum and joint tissues within 5 to 6 weeks of disease onset. These results provide an experimental model for studying the syndromes of KOA with dampness-heat obstruction syndrome.
Animals
;
Male
;
Rats, Sprague-Dawley
;
Rats
;
Osteoarthritis, Knee/physiopathology*
;
Disease Models, Animal
;
Humans
;
Interleukin-1beta/metabolism*
;
Interleukin-6/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Knee Joint/pathology*
9.Pharmacodynamics study and establishment of a PK-PD model for Epimedii Folium-Chuanxiong Rhizoma in treating osteoarthritis in rats.
En-Hui WU ; Jian-Hua ZHANG ; Wen-Jun CHEN ; Ya-Hong WANG ; Hua YIN
China Journal of Chinese Materia Medica 2025;50(5):1377-1384
This study aims to reveal the correlation between the pharmacokinetics(PK) and pharmacodynamics(PD) of multiple components in Epimedii Folium-Chuanxiong Rhizoma and clarify the pharmacodynamic material basis and mechanism of this herb pair in treating osteoarthritis. The Hulth method was used to establish the rat model of osteoarthritis and plasma was collected at various time points after drug administration. The plasma concentrations of multiple components were measured. Enzyme-linked immunosorbent assay(ELISA) was used to measure the plasma concentrations of matrix metalloproteinase(MMP)-3, MMP-13, interleukin-1β(IL-1β), nitric oxide(NO), and tumor necrosis factor-α(TNF-α) as pharmacodynamic indicators. Self-defined weighting coefficients were used to calculate the PK and PD data, and a Sigmoid E_(max) fitting model was used to evaluate the synergistic effect of the compatibility of Epimedii Folium-Chuanxiong Rhizoma. The PK-PD models for Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma were E=(1.926×C~(2.652))/(0.136 6~(2.652)+C~(2.652)), E=(1.618×C~(345.2))/(0.118 4~(345.2)+C~(345.2)), and E=(2.305×C~(2.786))/(0.240 3~(2.786)+C~(2.786)), respectively. The E_(max) of Epimedii Folium-Chuanxiong Rhizoma was larger than those of the two herbal medicines alone. The EC_(50) of the herb pair was lower than the sum of Epimedii Folium and Chuanxiong Rhizoma alone. The concentrations of MMP-3, MMP-13, IL-1β, NO, and TNF-α were correlated with mass concentrations of multiple components in Epimedii Folium and Chuanxiong Rhizoma, and the compatibility was better than single use. Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma may play a role in the treatment of osteoarthritis by inhibiting MMP-3, MMP-13, IL-1β, NO, and TNF-α.
Animals
;
Rats
;
Drugs, Chinese Herbal/pharmacology*
;
Male
;
Rats, Sprague-Dawley
;
Osteoarthritis/metabolism*
;
Epimedium/chemistry*
;
Interleukin-1beta/blood*
;
Tumor Necrosis Factor-alpha/blood*
;
Disease Models, Animal
;
Nitric Oxide/blood*
;
Humans
;
Rhizome/chemistry*
10.Mechanism of Syngnathus extract in treating knee osteoarthritis of rats via regulating PI3K/Akt/mTOR signaling pathway.
Quan-Wei ZHENG ; Guo-Wei WANG ; Si-Xian WU ; Tao ZHUO ; Yi HE ; Jian-Hang LIU
China Journal of Chinese Materia Medica 2025;50(9):2442-2449
To investigate the mechanism of action of Syngnathus extract in treating knee osteoarthritis of rats, forty-eight male SD rats were randomly divided into the blank group, model group, positive drug group, as well as low-dose, medium-dose, and high-dose groups of Syngnathus extract. The rat model of knee osteoarthritis was constructed by intra-articular injection of sodium iodoacetate. After successful modeling, celecoxib(18 mg·kg~(-1)·d~(-1)) and Syngnathus extract(0.4, 0.8, and 1.6 g·kg~(-1)·d~(-1)) were given in different groups by gavage intervention for two weeks. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of cartilage in knee joints, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of inflammatory factors in serum. Real-time fluorescence quantitative PCR, Western blot, and immunohistochemistry were used to detect the levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target protein of rapamycin(mTOR) pathway-related mRNA and protein expression. The results showed that, comparied with the blank group, the cartilage surface of the knee joints of rats in the model group was uneven, with disorganized levels and defective cartilage tissue. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) and the mRNA levels of PI3K, Akt, and mTOR in cartilage tissue, as well as the protein expression levels of phosphorylated PI3K(p-PI3K)/PI3K, phosphorylated Akt(p-Akt)/Akt, phosphorylated mTOR(p-mTOR)/mTOR, and P62 were significantly increased. Beclin1 protein expression was decreased. Comparied with the model group, the number of chondrocytes in the knee joint of rats in each group of Syngnathus extract increased, and the arrangement of chondrocytes was relatively neat. The cartilage layer was restored, and the serum levels of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of PI3K, Akt, and mTOR in cartilage tissue were significantly reduced. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and P62 were significantly reduced in the rats in the middle-dose and high-dose groups of Syngnathus extract, and the Beclin1 protein expression was significantly increased. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and P62 in rats in the low-dose group of Syngnathus extract were significantly reduced. In summary, Syngnathus extract may be used to treat knee osteoarthritis by inhibiting the expression of PI3K/Akt/mTOR signaling pathway, so as to alleviate the inflammatory response in the organism, enhance the autophagy activity of chondrocytes, and reduce the apoptosis of chondrocytes.
Animals
;
TOR Serine-Threonine Kinases/genetics*
;
Male
;
Rats, Sprague-Dawley
;
Signal Transduction/drug effects*
;
Proto-Oncogene Proteins c-akt/genetics*
;
Rats
;
Osteoarthritis, Knee/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Humans

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