Computed tomography radiomics in predicting patient satisfaction after robotic-assisted total knee arthroplasty.

PURPOSE: After robotic-assisted total knee arthroplasty (RA-TKA) surgery, some patients still experience joint discomfort. We aimed to establish an effective machine learning model that integrates radiomic features extracted from computed tomography (CT) scans and relevant clinical information to predict patient satisfaction three months postoperatively following RA-TKA. MATERIALS AND METHODS: After careful selection, data from 142 patients were randomly divided into a training set (n = 99) and a test set (n = 43), approximately in a 7:3 ratio. A total of 1329 radiomic features were extracted from the regions of interest delineated in CT scans. The features were standardized using normalization algorithms, and the least absolute shrinkage and selection operator regression model was employed to select radiomic features with ICC > 0.75 and P < 0.05, generating the Rad-score as feature markers. Univariate and multivariate logistic regression was then used to screen clinical information (age, body mass index, operation time, gender, surgical side, comorbidities, preoperative KSS score, preoperative range of motion (ROM), preoperative and postoperative HKA angle, preoperative and postoperative VAS score) as potential predictive factors. The satisfaction scale ≥ 20 indicates patient satisfaction. Finally, three prediction models were established, focusing on radiomic features, clinical features, and their fusion. Model performance was evaluated using Receiver Operating Characteristic curves and decision curve analysis. RESULTS: In the training set, the area under the curve (AUC) of the clinical model was 0.793 (95% CI 0.681-0.906), the radiomic model was 0.854 (95% CI 0.743-0.964), and the combined radiomic-clinical model was 0.899 (95% CI 0.804-0.995). In the test set, the AUC of the clinical model was 0.908 (95% CI 0.814-1.000), the radiomic model was 0.709 (95% CI 0.541-0.878), and the combined radiomic-clinical model was 0.928 (95% CI 0.842-1.000). The AUC of the radiomic-clinical model was significantly higher than the other two models. The decision curve analysis indicated its clinical application value. CONCLUSION: We developed a radiomic-based nomogram model using CT imaging to predict the satisfaction of RA-TKA patients at 3 months postoperatively. This model integrated clinical and radiomic features and demonstrated good predictive performance and excellent clinical application potential.

Corrigendum: Bioinformatic analysis of related immune cell infiltration and key genes in the progression of osteonecrosis of the femoral head.

[This corrects the article DOI: 10.3389/fimmu.2023.1340446.].

Dehydroandrographolide alleviates rheumatoid arthritis by inhibiting neutrophil activation via LMIR3 in collagen induced arthritis rats.

Rheumatoid arthritis (RA) is an inflammatory disease which causes severe pain and disability. Neutrophils play essential roles in the onset and progression of RA; thus, inhibition of neutrophil activation is becoming a popular therapeutic strategy. Dehydroandrographolide has provided satisfactory outcomes in inflammatory diseases; however, its therapeutic effects and mechanism in RA are not fully understood. Leukocyte mono-immunoglobulin-like receptor 3 (LMIR3) is a negative regulator highly expressed in neutrophils. To determine whether dehydroandrographolide negatively regulated neutrophils activation via LMIR3, cytokines release and collagen-induced arthritis (CIA) rats were used in vitro and in vivo. Biacore, molecular docking analysis and molecular dynamics simulation were performed to prove the target of dehydroandrographolide. Moreover, the downstream signaling pathways of LMIR3 activation were analyzed by western blotting. Results showed that oral dehydroandrographolide administration of 2 mg/kg/day to CIA rats attenuated synovitis and bone and cartilage damage after the 28-day intervention, revealed using HE sections and micro-CT. Dehydroandrographolide significantly inhibited cytokine release and chemotaxis of LPS/TNF-α-activated neutrophils in vitro. Dehydroandrographolide inhibited neutrophils activation via binding to LMIR3. Moreover, dehydroandrographolide up-regulated the phosphorylation of SHP-1 and SHP-2, which are the essential kinases in the LMIR3 signaling pathways. This study revealed that dehydroandrographolide attenuated collagen-induced arthritis by suppressing neutrophil activation via LMIR3.

[Melatonin promotes osteogenesis of bone marrow mesenchymal stem cells by improving the inflammatory state in ovariectomized rats].

Objective: To investigate the effects of melatonin (MT) on bone mass and serum inflammatory factors in rats received ovariectomy (OVX) and to investigate the effects of MT on the levels of inflammatory factors in culture medium and osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) stimulated by lipopolysaccharide. Methods: Fifteen 12-week-old Sprague Dawley (SD) rats were randomly divided into 3 groups. The rats in Sham group only received bilateral lateral abdominal incision and suture, the rats in OVX group received bilateral OVX, and the rats in OVX+MT group received 100 mg/(kg·d) MT oral intervention after bilateral OVX. After 8 weeks, the levels of serum inflammatory factors [interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α)] were detected using ELISA assay. Besides, the distal femurs were detected by Micro-CT to observe changes in bone mass and microstructure, and quantitatively measured bone volume fraction, trabecular thickness, and trabecular number. The BMSCs were extracted from the femurs of three 3-week-old SD rats using whole bone marrow culture method and passaged. The 3rd-5th passage BMSCs were cultured with different concentrations of MT (0, 1, 10, 100, 1 000 µmol/L), and the cell viability was then detected using cell counting kit 8 (CCK-8) to select the optimal concentration of MT for subsequent experiments. Cells were devided into osteogenic induction group (group A) and osteogenic induction+1/5/10 µg/mL lipopolysaccharide group (group B-D). The levels of inflammatory factors (IL-1ß, IL-6 and TNF-α) in cell culture medium were detected using ELISA assay after corresponding intervention. According to the results of CCK-8 method and ELISA detection, the cells were intervened with the most significant concentration of lipopolysaccharide for stimulating inflammation and the optimal concentration of MT with osteogenic induction, defining as group E, and the cell culture medium was collected to detect the levels of inflammatory factors by ELISA assay. After that, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively in groups A, D, and E, and the expression levels of osteogenic related genes [collagen type Ⅰ alpha 1 chain (Col1a1) and RUNX family transcription factor 2 (Runx2)] were also detected by real time fluorescence quantitative PCR (RT-qPCR). Results: ELISA and Micro-CT assays showed that compared with Sham group, the bone mass of the rats in the OVX group significantly decreased, and the expression levels of serum inflammatory factors (IL-1ß, IL-6, and TNF-α) in OVX group significantly increased (P<0.05). Significantly, the above indicators in OVX+MT group were all improved (P<0.05). Rat BMSCs were successfully extracted, and CCK-8 assay showed that 100 µmol/L was the maximum concentration of MT that did not cause a decrease in cell viability, and it was used in subsequent experiments. ELISA assays showed that compared with group A, the expression levels of inflammatory factors (IL-1ß, IL-6, and TNF-α) in the cell culture medium of groups B-D were significantly increased after lipopolysaccharide stimulation (P<0.05), and in a concentration-dependent manner. Moreover, the expression levels of inflammatory factors in group D were significantly higher than those in groups B and C (P<0.05). After MT intervention, the expression levels of inflammatory factors in group E were significantly lower than those in group D (P<0.05). ALP staining, alizarin red staining, and RT-qPCR assays showed that compared with group A, the percentage of positive area of ALP and alizarin red and the relative mRNA expressions of Col1a1 and Runx2 in group D significantly decreased, while the above indicators in group E significantly improved after MT intervention (P<0.05). Conclusion: MT may affect the bone mass of postmenopausal osteoporosis by reducing inflammation in rats; MT can reduce the inflammation of BMSCs stimulated by lipopolysaccharide and weaken its inhibition of osteogenic differentiation of BMSCs.

Learning curve and short-term clinical outcomes of a new seven-axis robot-assisted total knee arthroplasty system: a propensity score-matched retrospective cohort study.

OBJECTIVE: The purpose of the present study was to determine the learning curve for a novel seven-axis robot-assisted (RA) total knee arthroplasty (TKA) system and to explore whether it could provide superior short-term clinical and radiological outcomes compared with conventional surgery. METHODS: In the present retrospective study, 90 patients who underwent RA-TKA were included in robot-assisted system (RAS) group and 90 patients who underwent conventional TKA were included in the conventional group. The duration of surgery and robot-related complications were recorded to evaluate the learning curve through cumulative sum and risk-adjusted cumulative sum methods. The demographic data, preoperative clinical data, preoperative imaging data, duration of surgery, alignment of the prosthesis, lower limb force line alignment, Knee Society score, 10-cm visual analog scale pain score and range of motion were compared between the RAS and conventional groups. In addition, the proficiency group was compared with the conventional group using propensity score matching. RESULTS: RA-TKA was associated with a learning curve of 20 cases for the duration of surgery. There was no significant difference in indicators representing the accuracy of the prosthetic installation between the learning and proficiency phases in RA-TKA group patients. A total of 49 patients in the proficiency group were matched with 49 patients from the conventional group. The number of postoperative hip-knee-ankle (HKA) angle, component femoral coronal angle (CFCA), component tibial coronal angle (CTCA), and sagittal tibial component angle (STCA) outliers in the proficiency phase was lower than that in the conventional group, while deviations of the HKA angle, CFCA, CTCA, and STCA in the proficiency phase were significantly lower than those in the conventional group (P < 0.05). CONCLUSION: In summary, from the learning curve data, 20 cases are required for a surgeon using a novel seven-axis RA-TKA system to enter the proficiency phase. In the proficiency group, compared with the conventional group using propensity score matching, the RAS was found to be superior to the conventional group in prosthesis and lower limb alignment.

Prediction of early functional outcomes in patients after robotic-assisted total knee arthroplasty: a nomogram prediction model.

BACKGROUND: Robotic-assisted total knee arthroplasty (RA-TKA) is becoming more and more popular as a treatment option for advanced knee diseases due to its potential to reduce operator-induced errors. However, the development of accurate prediction models for postoperative outcomes is challenging. This study aimed to develop a nomogram model to predict the likelihood of achieving a beneficial functional outcome. The beneficial outcome is defined as a postoperative improvement of the functional Knee Society Score (fKSS) of more than 10 points, 3 months after RA-TKA by early collection and analysis of possible predictors. METHODS: This is a retrospective study on 171 patients who underwent unilateral RA-TKA at our hospital. The collected data included demographic information, preoperative imaging data, surgical data, and preoperative and postoperative scale scores. Participants were randomly divided into a training set ( N =120) and a test set ( N =51). Univariate and multivariate logistic regression analyses were employed to screen for relevant factors. Variance inflation factor was used to investigate for variable collinearity. The accuracy and stability of the models were evaluated using calibration curves with the Hosmer-Lemeshow goodness-of-fit test, consistency index and receiver operating characteristic curves. RESULTS: Predictors of the nomogram included preoperative hip-knee-ankle angle deviation, preoperative 10-cm Visual Analogue Scale score, preoperative fKSS score and preoperative range of motion. Collinearity analysis with demonstrated no collinearity among the variables. The consistency index values for the training and test sets were 0.908 and 0.902, respectively. Finally, the area under the receiver operating characteristic curve was 0.908 (95% CI 0.846-0.971) in the training set and 0.902 (95% CI 0.806-0.998) in the test set. CONCLUSION: A nomogram model was designed hereby aiming to predict the functional outcome 3 months after RA-TKA in patients. Rigorous validation showed that the model is robust and reliable. The identified key predictors include preoperative hip-knee-ankle angle deviation, preoperative visual analogue scale score, preoperative fKSS score, and preoperative range of motion. These findings have major implications for improving therapeutic interventions and informing clinical decision-making in patients undergoing RA-TKA.

Melatonin promotes the restoration of bone defects via enhancement of miR-335-5p combined with inhibition of TNFα/NF-κB signaling.

Accelerating the repair of a bone defect is crucial clinically due to the increased prevalence of trauma, tumor, and infections in bone. Studies have found that excess acute and chronic inflammation attenuate osteogenic differentiation of BMSCs (bone marrow mesenchymal stem cells). Moreover, TNF-α and NF-κB could inhibit osteoblasts differentiation of BMSCs and promote osteoclastogenesis via multiple mechanisms, such as increasing osteoclast precursor cells and acting synergistically with cell cytokines. However, melatonin could inhibit the expression of TNFα/NF-κB and promote bone formation by activating the Wnt/ß-catenin signaling pathway. However, there has been no evidence regarding the effect of melatonin on TNFα/NF-κB-inhibited osteoblastogenesis and bone formation. This study aimed to investigate the role of melatonin on TNFα/NF-κB-inhibited osteoblastogenesis and bone formation. Micro-CT, high-throughput screening, overexpression, and other methods were used, and we found that the number of osteoblasts was elevated with melatonin treatment. Additionally, TNFα/NF-κB signaling was inhibited, while miR-335-5p expression increased markedly following treatment with melatonin. Furthermore, miR-335-5p negatively regulated TNFα/NF-κB signaling, while miR-335-5p inhibitor ameliorated the effects of melatonin on TNFα/NF-κB. In conclusion, melatonin facilitates osteogenesis in bone defect healing by enhancing miR-335-5p expression and inhibiting the TNFα/NF-κB pathway.

Bioinformatic analysis of related immune cell infiltration and key genes in the progression of osteonecrosis of the femoral head.

Objective: Osteonecrosis of the femoral head (ONFH) is a common orthopedic condition that will prompt joint dysfunction, significantly impacting patients' quality of life. However, the specific pathogenic mechanisms underlying this disease remain elusive. The objective of this study is to examine the differentially expressed messenger RNAs (DE mRNAs) and key genes linked to ONFH, concurrently investigating the immune cell infiltration features in ONFH patients through the application of the CIBERSORT algorithm. Methods: Microarray was applied to scrutinize mRNA expression profiles in both ONFH patients and healthy controls, with data integration sourced from the GEO database. DE mRNAs were screened using the Limma method. The biological functions of DE mRNAs were explored through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Ontology (GO) functional analysis, and Gene Set Enrichment Analysis (GSEA). Additionally, support vector machine-recursive feature elimination (SVM-RFE) and the least absolute shrinkage and selection operator (LASSO) were employed to discern diagnostic biomarkers associated with the disease. Receiver operating characteristic (ROC) analysis was utilized to assess the statistical performance of the feature genes. The validation of key genes was performed using qRT-PCR in bone tissues obtained from ONFH patients and healthy controls. Osteogenic differentiation of BMSC was then performed and detected by alkaline phosphatase staining (ALP) and qRT-PCR to verify the correlation between key genes and osteogenic differentiation. Finally, immune cell infiltration analysis was executed to evaluate immune cell dysregulation in ONFH, concurrently exploring the correlation between the infiltration of immune cells and key genes. Results: After consolidating the datasets, the Limma method revealed 107 DEGs, comprising 76 downregulated and 31 upregulated genes. Enrichment analysis revealed close associations of these DE mRNAs with functions such as cell migration, osteoblast differentiation, cartilage development and extracellular region. Machine learning algorithms further identified APOD, FBXO43 and LRP12 as key genes. ROC curves demonstrated the high diagnostic efficacy of these genes. The results of qRT-PCR showed that the expression levels of key genes were consistent with those of microarray analysis. In addition, the results of in vitro experiments showed that APOD was closely related to osteogenic differentiation of BMSC. Immune infiltration analysis suggested a close correlation between ONFH and imbalances in levels of Neutrophils, Monocytes, Macrophages M2, Dendritic cells activated and Dendritic cells resting. Conclusion: APOD is closely related to osteogenic differentiation of BMSCs and can be used as a diagnostic marker of ONFH. Immune cell infiltration significantly differs between controls and ONFH patients.

Astragalin mitigates inflammatory osteolysis by negatively modulating osteoclastogenesis via ROS and MAPK signaling pathway.

Inflammatory bone destruction has gradually attracted attention worldwide and has been observed in several kinds of pathological bone diseases, such as osteoarthritis, osteomyelitis, rheumatic arthritis, and other infectious clinical trials in the skeletal system. In this regard, excessive osteoclasts and bone resorption activity participate in osteolytic processes. Thus, negatively modulating osteoclast differentiation and bone erosion has been considered an effective therapeutic strategy to limit the poor progression of inflammatory osteolysis. Astragalin (AST) is a bioactive component of traditional Chinese drugs, such as Rosa agrestis, which presents anti-inflammatory and antioxidant effects. However, it is unclear how AST may play an essential role in regulating the dynamic balance of the bone matrix by affecting osteoclastogenesis. This study found that AST could inhibit osteoclastic formation and bone resorption activity in a dose-dependent manner without cytotoxicity. Administration of AST also inhibited the expression of cathepsin K, c-Fos, NFATc1, and TRAP at different stages of mRNA and protein levels during osteoclastogenesis. Reactive oxygen species (ROS) signalling could also be modulated by treatment with AST during RANKL-induced osteoclast differentiation through the Nrf2-HO1 signalling pathway. Additionally, AST could negatively regulate mitogen-activated protein kinase (MAPK) signalling in this process. In vivo, AST significantly reduced lipopolysaccharide (LPS)-induced bone loss in an osteolytic mouse model. AST might be a promising therapeutic candidate for treating osteolytic bone diseases in the future.

Osteogenesis-Related Long Noncoding RNA GAS5 as a Novel Biomarker for Osteonecrosis of Femoral Head.

Background: The lack of effective biomarkers makes it difficult to achieve early diagnosis and intervention for osteonecrosis of the femoral head (ONFH). Hence, we aimed to identify novel long noncoding RNA (lncRNA) biomarkers for ONFH. Methods: High-throughput RNA sequencing was performed to detect lncRNA and mRNA expression levels in subchondral bone samples from three patients with ONFH and three patients with femoral neck fractures. Integrated bioinformatics analyses were conducted to identify lncRNAs associated with ONFH development and their potential functions and signaling pathways. A co-expression network was constructed based on the gene time-series expression data in GSE113253. After selecting lncRNA GAS5 as a novel biomarker for ONFH, bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation assays were performed to verify the association between lncRNA GAS5 and osteogenic differentiation. Alkaline phosphatase (ALP) staining and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to measure the osteogenic phenotype and lncRNA GAS5 expression. Finally, for further validation, ONFH rat models were established, and lncRNA GAS5 expression in subchondral bone was detected by RT-qPCR. Results: We identified 126 and 959 differentially expressed lncRNAs and genes, respectively. lncRNA GAS5 expression level was significantly downregulated in patients with ONFH compared to the control group patients. The BMSC osteogenic differentiation assays showed that ALP activity increased gradually from days 3 to 7, while the lncRNA GAS5 expression level was significantly upregulated in the osteogenic differentiation induction groups. Furthermore, in vivo experiments suggested that the bone volume/tissue volume value and trabecular thickness significantly decreased in the ONFH rat model group compared to the control group, whereas the trabecular space significantly increased in the ONFH group compared to the control group. In addition, the lncRNA GAS5 expression level significantly decreased in the ONFH rat model group. Conclusion: The lncRNA GAS5 expression level was highly associated with BMSC osteogenic differentiation and was significantly downregulated in both the subchondral trabecular bone tissue of ONFH patients and ONFH rat models. Therefore, lncRNA GAS5 can serve as an ONFH osteogenic biomarker to provide an effective target for early diagnosis and molecular therapy of ONFH.

An injectable self-adaptive polymer as a drug carrier for the treatment of nontraumatic early-stage osteonecrosis of the femoral head.

Core decompression (CD) with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head (ONFH). Adjuvant treatments are widely used in combination with CD as suitable methods of therapy. Existing augmentations have to be fabricated in advance. Here, we report a novel injectable glycerin-modified polycaprolactone (GPCL) that can adapt to the shape of the CD cavity. GPCL shows great flowability at 52.6 °C. After solidification, its compressive modulus was 120 kPa at body temperature (37 °C). This excellent characteristic enables the polymer to provide mechanical support in vivo. In addition, GPCL acts as a carrier of the therapeutic agent zoledronic acid (ZA), demonstrating sustained release into the CD region. ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases. Compared to that in the CD group, CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head. At the interface between the GPCL and CD tunnel wall, osteogenesis was significantly promoted. In addition, morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance. These results suggest a strategy effective to preserve the bone density of the femoral head, thus decreasing the possibility of femoral head collapse. This novel injectable polymer has, therefore, considerable potential in clinical applications.

Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis.

BACKGROUND: Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. METHODS: Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. RESULTS: Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 µmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. CONCLUSIONS: Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.

Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro.

BACKGROUND: Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. METHODS: Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-ß1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson's trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. RESULTS: The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-ß1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-ß1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-ß1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson's trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. CONCLUSIONS: PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.