OBJECTIVES: To assess the therapeutic effect of aucubin in mice with knee osteoarthritis (KOA) and investigate the underlying mechanism. METHODS: Sixty C57BL/6J mice were randomized equally into sham operation group, KOA model group, glucosamine (positive control) treatment group, and low-, medium-, and high-dose aucubin treatment groups (2, 4, and 8 mg/kg, respectively). KOA mouse models were established by transection of the anterior cruciate ligament (ACL), and the treatment was initiated on day 1 postoperatively and administered weekly for 8 weeks. Safranin O-fast green staining, immunohistochemistry, and microCT were used to evaluate the changes in cartilage pathology, inflammatory protein expression, and subchondral bone volume fraction (BV/TV). The expression levesl of COL2, SOX9, p-P65, IL-1β and MMP13 proteins in the cartilage tissues were detected using Western blotting. In a chondrocyte model with IL-1β treatment for mimicking KOA, the effect of aucubin on chondrogenic differentiation was observed with Alcian blue and Safranin O staining, and cellular COL2, SOX9 and TNF‑α mRNA expressions were detected with RT-qPCR. RESULTS: Compared with those in the model group, the mouse models receiving aucubin treatment showed significantly upregulated COL2 and SOX9 protein levels and downregulated p-P65, IL-1β and MMP13 expressions in the cartilage tissues. In the IL-1β-induced chondrocyte model, aucubin treatment significantly upregulated the mRNA expressions of SOX9 and COL2 but lowered the mRNA expression of TNF-α. Alcian blue and Safranin O staining confirmed that aucubin promoted the synthesis of cartilage extracellular matrix and enhanced chondrogenic differentiation of the cells. CONCLUSIONS Aucubin can effectively alleviate KOA in mice by inhibiting NF‑κB-mediated cartilage inflammation, promoting cartilage matrix synthesis, and improving subchondral bone microstructure.
Animals ; Mice, Inbred C57BL ; Mice ; Osteoarthritis, Knee/drug therapy* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Iridoid Glucosides/therapeutic use* ; SOX9 Transcription Factor/metabolism* ; Chondrocytes/drug effects* ; Male ; Interleukin-1beta/metabolism* ; Matrix Metalloproteinase 13/metabolism* ; Collagen Type II/metabolism* ; Disease Models, Animal

OBJECTIVE: To evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities. METHODS: The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score. RESULTS: There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05). CONCLUSION Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Robotic Surgical Procedures/methods* ; Male ; Female ; Retrospective Studies ; Range of Motion, Articular ; Middle Aged ; Aged ; Treatment Outcome ; Osteotomy/methods* ; Knee Joint/physiopathology* ; Operative Time

OBJECTIVE: To measure and analyze the relationships among the posterior tibial slope (PTS), meniscal slope (MS), and meniscus posterior horn thickness (MPHT) of the medial and lateral tibial plateau in healthy people and patients with anteromedial osteoarthritis (AMOA) in Heilongjiang province, so as to provide reference basis for appropriate tibial osteotomy and prosthesis placement angles in knee joint surgeries. METHODS: A retrospective collection of imaging data from knee joint MRI examinations conducted prior to AMOA for various reasons was performed. A total of 103 healthy individuals (healthy group) and 30 AMOA patients (AMOA group) were included. There was no significant difference in the gender composition ratio, side, and body mass index between the two groups ( P>0.05); however, the comparison of ages between the two groups showed a significant difference ( P<0.05). The collected DICOM format image data was imported into the RadiAnt DICOM Viewer software and measured the medial PTS (MPTS), lateral PTS (LPTS), medial MS (MMS), lateral MS (LMS), medial MPHT (MMPHT), and lateral MPHT (LMPHT) with standard methods. The differences of the above indexes between the two groups and between different genders and sides in the two groups were compared, and Pearson correlation analysis was carried out. At the same time, the measured data of healthy group were compared with the relevant literature reported in the past. RESULTS: Compared to the healthy group, the AMOA group exhibited significantly smaller MPTS and LPTS, as well as significantly greater MMPHT and LMPHT, with significant differences ( P<0.05). However, there was no significant difference in the MMS and LMS between the two groups ( P>0.05). The differences in various indicators between genders and sides within the two groups were not significant ( P>0.05). The correlation analysis and regression curves indicated that both MPTS and LPTS in the two groups were positively correlated with their respective ipsilateral MS and MPHT ( P<0.05); as PTS increased, the rate of increase in MS and MPHT tend to plateau. Compared to previous related studies, the MPTS and LPTS measured in healthy group were comparable to those of the Turkish population, exhibiting smaller values than those reported in other studies, while MMS and LMS were relatively larger, and MMPHT and LMPHT were smaller. CONCLUSION In healthy people and AMOA patients in Heilongjiang province, PTS has great individual differences, but there is no significant individual difference in MS. MPHT can play a certain role in retroversion compensation, and its thickness increase may be used as one of the indicators to predict the progression of AMOA. The above factors should be taken into account when UKA is performed, and the posterior tilt angle of tibial osteotomy should be set reasonably after preoperative examination and evaluation.
Humans ; Osteoarthritis, Knee/surgery* ; Retrospective Studies ; Tibia/pathology* ; Male ; Female ; Adult ; Menisci, Tibial/anatomy & histology* ; China ; Knee Joint/pathology* ; Magnetic Resonance Imaging ; Middle Aged ; Aged ; Osteotomy

OBJECTIVE: To investigate the effectiveness of digital three-dimensional (3D) printing osteotomy guide plate assisted total knee arthroplasty (TKA) in treatment of knee osteoarthritis (KOA) patients with femoral internal implants. METHODS: The clinical data of 55 KOA patients who met the selection criteria between July 2021 and October 2023 were retrospectively analyzed. Among them, 26 cases combined with femoral implants were treated with digital 3D printing osteotomy guide plate assisted TKA (guide plate group), and 29 cases were treated with conventional TKA (control group). There was no significant difference in gender, age, body mass index, side, Kellgren-Lawrence classification, preoperative visual analogue scale (VAS) score, Hospital for Special Surgery (HSS) knee score, knee range of motion, and other baseline data between the two groups ( P>0.05). The operation time, intraoperative blood loss, incision length, postoperative first ambulation time, surgical complications; VAS score, knee HSS score, knee range of motion before operation, at 1 week and 3 months after operation, and at last follow-up; distal femoral lateral angle, proximal tibial medial angle, hip-knee-ankle angle and other imaging indicators at last follow-up were recorded and compared between the two groups. RESULTS: The operation time, incision length, intraoperative blood loss, and postoperative first ambulation time in the guide plate group were significantly lower than those in the control group ( P<0.05). In the control group, there were 1 case of incision rupture and bleeding and 1 case of lower limb intermuscular venous thrombosis, which was cured after symptomatic treatment. There was no complication such as neurovascular injury, incision infection, or knee prosthesis loosening in both groups. Patients in both groups were followed up 12-26 months, with an average of 16.25 months. The VAS score, HSS score, and knee range of motion improved at each time point after operation in both groups, and further improved with time after operation, the differences were significant ( P<0.05). The above indicators in the guide plate group were significantly better than those in the control group at 1 week and 3 months after operation ( P<0.05), and there was no significant difference between the two groups at last follow-up ( P>0.05). At last follow-up, the distal femoral lateral angle, the proximal tibial medial angle, and the hip-knee-ankle angle in the guide plate group were significantly better than those in the control group ( P<0.05). CONCLUSION The application of digital 3D printing osteotomy guide plate assisted TKA in the treatment of KOA patients with femoral implants can simplify the surgical procedures, overcome limitations of conventional osteotomy guides, reduce surgical trauma, achieve individualized and precise osteotomy, and effectively restore lower limb alignment and knee joint function.
Humans ; Arthroplasty, Replacement, Knee/instrumentation* ; Osteoarthritis, Knee/surgery* ; Osteotomy/instrumentation* ; Male ; Retrospective Studies ; Female ; Printing, Three-Dimensional ; Femur/surgery* ; Middle Aged ; Bone Plates ; Range of Motion, Articular ; Aged ; Treatment Outcome ; Surgery, Computer-Assisted/methods* ; Knee Prosthesis ; Knee Joint/surgery* ; Operative Time

OBJECTIVE: To investigate the impact of bone mass and volume of low-density zones beneath the tibial plateau on the maximum von Mises stresses experienced by the cartilage and meniscus in the knee joint. METHODS: The study included one healthy adult volunteer, from whom CT scans were obtained, and one patient diagnosed with knee osteoarthrisis (KOA), for whom X-ray films were acquired. A static model of the knee joint featuring a low-density zone was established based on a normal knee model. In the finite element analysis, axial loads of 1 000 N and 1 800 N were applied to the weight-bearing region of the upper surface of the femoral head for model validation and subsequent finite element studies, respectively. The maximum von Mises stresses in the femoral cartilage, as well as the medial and lateral tibial cartilage and menisci, were observed, and the stress percentage of the medial and lateral components were concurrently analyzed. Additionally, HE staining, as well as alkaline magenta staining, were performed on the pathological specimens of patients with KOA in various low-density regions. RESULTS: The results of model validation indicated that the model was consistent with normal anatomical structures and correlated with previous calculations documented in the literature. Static analysis revealed that the maximum von Mises stress in the medial component of the normal knee was the lowest and increased with the advancement of the hypointensity zone. In contrast, the lateral component exhibited an opposing trend, with the maximum von Mises stress in the lateral component being the highest and decreasing as the hypointensity zone progressed. Additionally, the medial component experienced an increasing proportion of stress within the overall knee joint. HE staining demonstrated that the chondrocyte layer progressively deteriorated and may even disappear as the hypointensity zone expanded. Furthermore, alkaline magenta staining indicated that the severity of microfractures in the trabecular bone increased concurrently with the expansion of the hypointensity zone. CONCLUSION The presence of subtalar plateau low-density zone may aggravate joint degeneration. In clinical practice, it is necessary to pay attention to the changes in the subtalar plateau low-density zone and actively take effective measures to strengthen the bone status of the subtalar plateau low-density zone and restore the complete biomechanical function of the knee joint, in order to slow down or reverse the progression of osteoarthritis.
Humans ; Finite Element Analysis ; Knee Joint/physiology* ; Tibia/anatomy & histology* ; Cartilage, Articular/physiology* ; Menisci, Tibial/physiopathology* ; Tomography, X-Ray Computed ; Osteoarthritis, Knee/diagnostic imaging* ; Weight-Bearing ; Bone Density ; Adult ; Stress, Mechanical ; Male ; Middle Aged ; Biomechanical Phenomena ; Female

OBJECTIVE: To investigate the effect of femoral condyle sliding osteotomy (FCSO) on the flexion gap and external rotation of the prosthesis in balancing coronal instability during initial total knee arthroplasty (TKA). METHODS: Between November 2021 and October 2024, FCSO technique was applied to balance the coronal medial and lateral spaces during initial TKA in 3 patients, including medial condyle sliding osteotomy (MCSO) and lateral condyle sliding osteotomy (LCSO). There were 1 male and 2 females with the age of 81, 68, and 68 years old. The affected knee has varus or valgus deformity, with tibia-femoral angles of 169.7°, 203.3°, and 162.2°, respectively. The hip-knee-ankle angle (HKA), range of motion (ROM), knee society scoring system (KSS), and pain visual analogue scale (VAS) score were used to evaluate joint function and pain relief. Based on model bone, the thickness and bone bed area of the medial and lateral femoral condyle osteotomy blocks in FCSO were measured. During TKA in 12 patients, the range of osteotomy block movement was evaluated. By simplifying the upward and forward movement of the osteotomy block into a geometric model, the impact of movement on the flexion gap and external rotation of the prosthesis was calculated. RESULTS: After application of FCSO during TKA, the limb alignment and medial and lateral balance at extension and flexion positions were restored in 3 patients. Three patients were followed up 23, 11, and 3 months, respectively. Postoperative HKA, pain VAS score, KSS score, and ROM all showed significant improvement compared to preoperative levels. The maximum thickness of osteotomy blocks by MCSO and LCSO was 17 and 12 mm, respectively. The simple upward movement of the osteotomy block mainly affected the extension gap, and had little effect on the flexion gap and external rotation of the prosthesis. Moving the osteotomy block forward at the same time had a significant impact on the flexion gap and external rotation of the prosthesis, especially on LCSO. Mild forward movement leaded to a decrease in external rotation of more than 3°, which had a serious impact on the patellar trajectory. CONCLUSION FCSO can effectively solve the problem of imbalance between the medial and lateral spaces during initial TKA, avoiding knee joint instability caused by excessive loosening and limiting the use of constrained condylar prosthesis. The distance for the downward movement of the osteotomy block in MCSO and LCSO was 3-5 mm and 6-8 mm, respectively, with 10-15 mm of space for forward movement and almost no space for backward movement. For MCSO, the upward and forward movement of the osteotomy block will increase the external rotation of the prosthesis, which is beneficial for improving the patellar trajectory and suitable for valgus knee. LCSO is suitable for varus knee, and the osteotomy block only slides vertically up and down without moving forward and backward.
Humans ; Osteotomy/methods* ; Male ; Female ; Arthroplasty, Replacement, Knee/methods* ; Aged ; Range of Motion, Articular ; Femur/surgery* ; Knee Joint/physiopathology* ; Aged, 80 and over ; Knee Prosthesis ; Treatment Outcome ; Osteoarthritis, Knee/surgery*

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

Objective To explore the effect of rehmanniae radix extract(RRE)on chondrocyte apoptosis in the rabbit model of knee osteoarthritis(KOA)by regulating the miR-485-5p/heat shock protein 90 beta family member 1(Hsp90b1)axis.Methods New Zealand rabbits were randomly assigned into control,KOA,low-dose RRE,medium-dose RRE,high-dose RRE,celecoxib,high-dose RRE+antagonist control,and high-dose RRE+miR-485-5p antagonist groups,with 12 rabbits in each group.Rabbits in other groups except the control group were modeled for KOA with the improved Hulth method.After modeling for 8 weeks,the rabbits were administrated with corresponding agents for 4 weeks.The changes in the activity rating of rabbits were recorded.ELISA was employed to measure the levels of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the serum.Safranine O-fast green staining was conducted to reveal the pathological changes in the cartilage tissue and Mankin scoring was performed.TUNEL was employed to detect chondrocyte apoptosis.Real-time fluorescence quantitative PCR was performed to determine the expression of miR-485-5p in the cartilage tissue.Western blot was employed to determine the protein levels of Hsp90b1,cleaved cysteinyl aspartate-specific proteinase-3(Caspase-3),and Bcl2-associated-X(Bax)in the cartilage tissue.The dual-luciferase reporter assay was employed to examine the relationship between miR-485-5p and Hsp90b1.Results Compared with the control group,the KOA group showed down-regulated expression of miR-485-5p,elevated levels of TNF-α and IL-6 in the serum,cartilage erosion and losses,and increases in activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.001).Compared with the KOA group,RRE at low,medium,and high doses,and celecoxib up-regulated the expression of miR-485-5p,lowered the levels of TNF-α and IL-6 in the serum,alleviated the pathological damage to the cartilage tissue,and decreased the activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.05).Compared with the high-dose RRE group and the high-dose RRE+antagonist control group,high-dose RRE+miR-485-5p antagonist down-regulated the expression of miR-485-5p,elevated the levels of TNF-α and IL-6 in the serum,exacerbated the pathological damage to the cartilage tissue,and increased the activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.05).The results indicated that there was a targeted regulatory relationship between miR-485-5p and Hsp90b1.Conclusion RRE may inhibit the expression of Hsp90b1 by up-regulating miR-485-5p,thereby inhibiting chondrocyte apoptosis in the rabbit model of KOA.
Animals ; Rabbits ; Apoptosis/drug effects* ; Chondrocytes/pathology* ; Osteoarthritis, Knee/drug therapy* ; MicroRNAs/metabolism* ; Rehmannia/chemistry* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/blood* ; Plant Extracts/pharmacology* ; Interleukin-6/blood* ; HSP90 Heat-Shock Proteins/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To observe the clinical effect of internal heat acupuncture therapy for knee osteoarthritis of early to middle stages, and explore its influence on cartilage thickness. METHODS: A total of 44 patients with knee osteoarthritis of early to middle stages were treated with internal heat acupuncture therapy at ashi points (most of them are located at the subpatellar fat pad, both sides of the patellar ligament, the tendon of the quadriceps and the attachment of the medial and lateral collateral ligaments), once a week, a total of 4 weeks of treatment. Before and after treatment, after 3 months of treatment completion (in the follow-up), the visual analogue scale (VAS) score, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score, frequency of 30-second chair stand test (30sCST), cartilage thickness of femoral intercondylar and knee joint ultrasound score were compared, and the clinical effect was evaluated. RESULTS: After treatment, the VAS、WOMAC and knee joint ultrasound scores were reduced (P<0.05), frequency of 30sCST was increased (P<0.05) compared with those before treatment; in the follow-up, the VAS、WOMAC scores were reduced (P<0.05), frequency of 30sCST and cartilage thickness of femoral intercondylar were increased (P<0.05) compared with those before treatment. After treatment, the total effective rate was 93.2% (41/44), in the follow-up, the total effective rate was 95.5% (42/44). CONCLUSION Internal heat acupuncture therapy is effective in the treatment of knee osteoarthritis of early to middle stages, could relieve the pain, improve the joint function, and delay cartilage degeneration and disease progression.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Aged ; Treatment Outcome ; Adult ; Acupuncture Points

Acupotomy therapy demonstrates the definite clinical efficacy on knee osteoarthritis (KOA). After reviewing systematically the mechanism studies on acupotomy for KOA over the past 5 years, It is revealed that acupotomy synergistically intervenes in the pathological progression of KOA through multi-target approaches, such as regulating cartilage homeostasis, restoring skeletal muscle function, alleviating synovial inflammatory responses, remodeling subchondral bone, and neuromodulation. But the current research still limits to single-tissue phenotypic observation, and is insufficiency in the in-depth exploration of multi-tissue synergistic interactions and molecular upstream-downstream regulatory mechanisms. Future studies should focus on the inheritance and innovation of acupotomy theory, and integrating multi-omics analytical technologies, artificial intelligence, and novel biochemical detection methods. The mechanism research targets on the interaction mechanisms among tissues, direct effects of acupotomy, immune-inflammatory regulatory mechanisms, and analgesic mechanisms, so as to comprehensively elucidate the therapeutic mechanism of acupotomy for KOA.
Humans ; Acupuncture Therapy ; Osteoarthritis, Knee/genetics* ; Animals