Enhancing Cartilage Metabolism in Rats through a Novel Thermal Stimulation Technique with Photosensitizers.

Although the moderate thermal stimulation of articular cartilage exerts chondroprotective effects, it is difficult to effectively heat deep articular cartilage with conventional methods. Photosensitizers increase the ambient temperature using near-infrared (NIR) radiation, which has high tissue permeability. We hypothesized that the intra-articular administration of photosensitizers and NIR irradiation would exert a greater heating effect on articular cartilage. We aimed to evaluate the heating effect of this method on cultured chondrocytes and rat knee cartilage. In vitro, we irradiated a photosensitizer-containing medium with NIR and measured changes in the medium temperature, cytotoxicity, and gene expression of heat shock protein (HSP) 70 and aggrecan (ACAN). In vivo, the knee joints of rats treated with photosensitizers were irradiated with NIR, and changes in intra-articular temperature and gene expression were measured, alongside histological analysis. The results showed that the medium and intra-articular temperature were raised to approximately 40 °C with no apparent disruption to articular cartilage or the immunohistochemically enhanced staining of HSP70 in chondrocytes. The gene expression of HSP70 and ACAN was increased in both cultured and articular cartilage. In summary, this method can safely heat joints and enhance cartilage metabolism by inducing HSP70 expression in articular cartilage. It presents a new hyperthermia therapy with effective cartilage protection.

Hypoxia with or without Treadmill Exercises Affects Slow-Twitch Muscle Atrophy and Joint Destruction in a Rat Model of Rheumatoid Arthritis.

The effects of treadmill running under hypoxic conditions on joints and muscles of collagen-induced arthritis (CIA) rats were investigated. CIA rats were divided into normoxia no-exercise, hypoxia no-exercise (Hypo-no), and hypoxia exercise (Hypo-ex) groups. Changes were examined on days 2 and 44 of hypoxia with or without treadmill exercises. In the early stage of hypoxia, the expression of hypoxia-inducible factor (HIF)-1α increased in the Hypo-no and Hypo-ex groups. The expression of the egl-9 family hypoxia-inducible factor 1 (EGLN1) and vascular endothelial growth factor (VEGF) in the Hypo-ex group also increased. Under sustained hypoxia, the Hypo-no and Hypo-ex groups did not show increased expression of HIF-1α or VEGF, but p70S6K levels were elevated. Histologically, joint destruction was alleviated in the Hypo-no group, the loss of muscle weight in slow-twitch muscles was prevented, and muscle fibrosis was suppressed. In the Hypo-ex group, the preventive effect of a reduction in the slow-twitch muscle cross-sectional area was enhanced. Thus, chronic hypoxia in an animal model of rheumatoid arthritis controlled arthritis and joint destruction and prevented slow-twitch muscle atrophy and fibrosis. The combination of hypoxia with treadmill running further enhanced the preventive effects on slow-twitch muscle atrophy.

CD81 inhibition with the cytoplasmic RNA vector producing anti-CD81 antibodies suppresses arthritis in a rat CIA model.

OBJECTIVE: Cluster of differentiation 81 (CD81) is a tetraspanin membrane protein consisting of 4 transmembrane domains and 2 outer membrane loops. CD81 inhibition is a potential treatment for rheumatoid arthritis (RA). Here, we investigated the therapeutic effects of the cytoplasmic RNA vector expressing anti-CD81 antibodies (the anti-CD81 vector) on the ankle joint synovium in collagen-induced arthritis (CIA) rats. METHODS: Body weight, paw volume, and clinical scores were measured on days 0, 7, and 10 and daily thereafter. On day 28, the ankle joints of the rats were removed and stained with haematoxylin, eosin, and Safranin O. Arthritic changes such as inflammatory cell infiltration, synovial proliferation, articular cartilage destruction, and bone erosion were evaluated by histological scoring. RESULTS: Symptom onset was delayed in the right lower limbs of the rats administered the cytoplasmic RNA vector (CIA + anti-CD81) compared with that in the control group (CIA + control). The CIA + anti-CD81 rats were heavier than the CIA + control rats. The paw volume and clinical scores were significantly lower in the CIA + anti-CD81 than in the CIA + control. The histological scores indicated significantly milder manifestations of RA in the CIA + anti-CD81 than in the CIA + control. CONCLUSIONS: Administration of the cytoplasmic RNA vector expressing anti-CD81 antibodies suppressed arthritis and joint destruction in CIA rats. Our findings suggest that the cytoplasmic RNA vector can be used to treat RA.

Treadmill running prevents atrophy differently in fast- versus slow-twitch muscles in a rat model of rheumatoid arthritis.

To investigate the effects of treadmill running on two different types of skeletal muscle, we established a rat model of collagen-induced arthritis (CIA). The skeletal muscles studied were the extensor digitorum longus (EDL), which is rich in fast-twitch muscle fibers, and the soleus, which is rich in slow-twitch muscle fibers. The histological and transcriptional changes in these muscles at 14 and 44 days after immunosensitization were compared between rats that were forced to exercise (CIA ex group) and free-reared CIA rats (CIA no group). Change in protein expression was examined on day 14 after a single bout of treadmill running. Treadmill running had different effects on the relative muscle weight and total and fiber cross-sectional areas in each muscle type. In the soleus, it prevented muscle atrophy. Transcriptional analysis revealed increased eukaryotic translation initiation factor 4E (Eif4e) expression on day 14 and increased Atrogin-1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression on day 44 in the soleus in the CIA ex group, suggesting an interaction between muscle type and exercise. A single bout of treadmill running increased the level of Eif4e and p70S6K and decreased that of Atrogin-1 in the soleus on day 14. Treadmill running prevented muscle atrophy in the soleus in a rat model of rheumatoid arthritis via activation of mitochondrial function, as evidenced by increased PGC-1α expression.

Clinical outcomes after medial patellofemoral ligament reconstruction: an analysis of changes in the patellofemoral joint alignment.

PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction using the hamstring tendon is widely performed to treat recurrent patellar dislocation. MPFL reconstruction includes a post-operative process of necrosis and reperfusion of the hamstring tendon graft. We hypothesise that the patella gradually shifts laterally because of this process, ultimately affecting the patellofemoral joint alignment. This study aimed to analyse the chronological changes in the patellofemoral joint alignment and the outcomes of MPFL reconstruction. METHODS: In this retrospective case-series study, the Knee Society, Lysholm, and Kujala scores were evaluated in 24 consecutive patients (27 knees). To evaluate patellar tracking defects, radiographic indices including the tilting angle, the lateral shift ratio, and the congruence angle were measured before, immediately after, and three, 12, and 36 months after MPFL reconstruction. RESULTS: Post-operative Kujala, Knee Society, and Lysholm scores for the study population significantly improved relative to the pre-operative scores. The tilting and congruence angles at three months after the operation significantly increased relative to those recorded immediately after the operation. The tilting and congruence angles were not significantly different at three, 12, and 36 months after the operation. CONCLUSIONS: The post-operative outcomes of MPFL reconstruction for recurrent patellar dislocation were favourable. Insufficient union between the bone tunnel and tendon graft, along with an elongation of the necrotic tendon graft, may change the alignment of the patellofemoral joint within three months after the operation. Therefore, we believe it is necessary to refrain from knee rotation that places lateral stress on the patella until three months after the operation.

Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via Negative Feedback of Hypoxia Inducible Factor-1α.

Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h (p < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group (p < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression.

Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models.

Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.

Outcome of Low-Invasive Local Split-Thickness Lengthening for Iliotibial Band Friction Syndrome.

Conventional surgical methods for iliotibial band friction syndrome (ITBFS) may affect the iliotibial band (ITB), delaying return to sports activities or impeding performance. We have developed a minimally invasive method. This study retrospectively analyzed the outcomes of this procedure in individuals with ITBFS. This study included 34 knees of 31 individuals. Surgery involved lengthening the central part of the ITB by splitting it into a superficial and a deep layer, maintaining the anterior and posterior fibers immediately above the lateral epicondyle. Outcomes included time to resume sports activity, personal best times to run a 5000-m race before and after surgery, and 2-month post-surgery muscle strengths. The mean postoperative time to return to competition was 5.8 weeks. Personal best times of 5000-m race improved in 13 of 17 runners. Two months post-surgery, the mean extensor muscle strengths on the healthy and affected sides did not significantly differ nor did the flexor muscle strengths. In ITBFS, the ITB itself is normal. Lengthening the limited region of the ITB immediately above the lateral femoral epicondyle removes the cause of ITBFS, with a reduction in inflammation. This technique resulted in early return to competition without degrading performance.

Length change patterns and shape of a grafted tendon after anatomical medial patellofemoral ligament reconstruction differs from that in a healthy knee.

PURPOSE: Recurrent patellar dislocation is currently treated with anatomical reconstruction of the medial patellofemoral ligament (MPFL), and favourable postoperative outcomes have been reported. However, it is uncertain if healthy MPFL function is restored by anatomical reconstruction. The hypothesis in this study was that stabilization of the patella following MPFL reconstruction would be improved compared with that before surgery, but that function of the grafted tendon would differ from that of a healthy MPFL. The objective was to analyse the length change patterns of the MPFL before surgery and the grafted tendon after surgery in patients with recurrent patellar dislocation treated with anatomical MPFL reconstruction. METHODS: The subjects were 12 patients (13 knees) in whom recurrent patellar dislocation was treated with anatomical MPFL reconstruction. The length change patterns of the MPFL and reconstructed ligament were analysed at extension and flexion of the knee joint using open MRI. RESULTS: The postoperative grafted tendon length was significantly shorter than that of the preoperative MPFL at knee extension, and significantly longer at 90° and 120° of knee flexion. The postoperative length of the grafted tendon only changed slightly from 0° to 30° of knee flexion, and then significantly decreased at flexion of 30° or more. The morphology of the grafted tendon was linear until 60° knee flexion, but became convex toward the extraarticular side at flexion of 90° or more. CONCLUSION: The grafted tendon length at knee extension was shorter than that of the preoperative MPFL, but there was no significant difference at 30° flexion. These findings suggest that the effect of damping of the patella with a grafted tendon after MPFL reconstruction may differ from that in a healthy knee. In addition, the morphology at 60° knee flexion was improved to linear after surgery, suggesting that ligament morphology at this flexion was normalized by MPFL reconstruction. LEVEL OF EVIDENCE: III.

Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model.

We analyzed the influence of treadmill running on rheumatoid arthritis (RA) joints using a collagen-induced arthritis (CIA) rat model. Eight-week-old male Dark Agouti rats were randomly divided into four groups: The control group, treadmill group (30 min/day for 4 weeks from 10-weeks-old), CIA group (induced CIA at 8-weeks-old), and CIA + treadmill group. Destruction of the ankle joint was evaluated by histological analyses. Morphological changes of subchondral bone were analyzed by µ-CT. CIA treatment-induced synovial membrane invasion, articular cartilage destruction, and bone erosion. Treadmill running improved these changes. The synovial membrane in CIA rats produced a large amount of tumor necrosis factor-α and Connexin 43; production was significantly suppressed by treadmill running. On µ-CT of the talus, bone volume fraction (BV/TV) was significantly decreased in the CIA group. Marrow star volume (MSV), an index of bone loss, was significantly increased. These changes were significantly improved by treadmill running. Bone destruction in the talus was significantly increased with CIA and was suppressed by treadmill running. On tartrate-resistant acid phosphate and alkaline phosphatase (TRAP/ALP) staining, the number of osteoclasts around the pannus was decreased by treadmill running. These findings indicate that treadmill running in CIA rats inhibited synovial hyperplasia and joint destruction.

Comparative analysis of medial patellofemoral ligament length change pattern in patients with patellar dislocation using open-MRI.

PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction has become a common form of treatment for recurrent patellar dislocation. This study was performed using open-MRI to compare the length change pattern of MPFL in patients with a history of patellar dislocation to that in healthy subjects. METHODS: The subjects comprised 10 knees of 8 males and 13 knees of 12 females with a history of one or more patellar dislocations. The length of the MPFL was measured using open-MRI in both the leg-extended position and knee-flexed positions to analyse the length change pattern. RESULTS: The average MPFL lengths were 58.6 ± 6.5 mm and 52.0 ± 4.6 mm for males and females in the extended knee position, respectively. The length change pattern of the MPFL showed slight variation up to a flexion angle of 30° and a clear decrease above 30°. This pattern differed from that of normal MPFL. In terms of morphology, the fibre bundle of the damaged MPFL followed a convex course towards the side of the patellofemoral joint surface at a knee flexion angle of 60°, whereas that of the normal MPFL followed a straight course. CONCLUSION: The in vivo damaged MPFL length change pattern was specific and differed distinctly from that of normal MPFL. The results of the present study suggested that MPFL fibres with a history of patellar dislocation lack sufficient tension at knee flexion angles of 0°-60°. However, further studies are needed to obtain a better understanding of cases with a patellar dislocation or postsurgical cases of MPFL reconstruction. LEVEL OF EVIDENCE: III.

Assessing coronal laxity in extension and flexion at a minimum of 10 years after primary total knee arthroplasty.

PURPOSE: Favourable long-term results after total knee arthroplasty (TKA) require appropriate soft tissue balance. However, the relationships between long-term results after TKA surgery and mediolateral laxities at extension and at 90° flexion remain unknown. This study therefore quantitatively assessed ligament balance at extension and at 90° knee flexion at least 10 years after primary TKA, as well as clarifying the relationships between long-term outcomes and mediolateral laxities. METHODS: This study included 49 knees (19 CR type and 30 PS type) of 33 patients followed up for at least 10 years after TKA at our hospital. Plain radiographs were obtained with about 150 N of varus or valgus stress using a Telos arthrometer at extension. At 90° flexion, epicondylar views were obtained under a 1.5-kg load and with about 10 kg of varus or valgus stress. RESULTS: Lateral laxity of about 5° was observed in both extension and flexion, with total laxities of varus and valgus stress each less than 10°. Postoperative clinical outcomes were good, with significant improvements in extension angle, femorotibial angle, and KSS, and no loosening in any knee. CONCLUSIONS: Good long-term results of TKA can be obtained with a lateral laxity of about 5°, equivalent to that of healthy knees. LEVEL OF EVIDENCE: III.

Magnetic resonance angiography evaluation of the bone tunnel and graft following ACL reconstruction with a hamstring tendon autograft.

PURPOSE: In this study, magnetic resonance angiography (MRA) was performed in the early phase after anterior cruciate ligament (ACL) reconstruction to analyse the changes in nutrient blood vessels and blood flow to the femoral and tibial tunnels and the intraosseous tendon grafts. METHODS: The subjects were 30 patients who underwent single-bundle ACL reconstruction with an autogenous hamstring tendon. MRA was performed at 2, 3, and 6 months postoperatively (n = 10 at each time point). The mean overall signal-to-noise ratios (SNRs) in the tunnel regions and in the region of the tendon graft were compared in each femur and tibia. RESULTS: Blood vessels from arteries reached the femoral and tibial tunnels 2 months postoperatively. The tunnel walls showed high signal intensity, while the intraosseous tendon grafts had lower intensity. SNRs showed significant differences between the femoral and tibial tunnels overall and the intraosseous tendon grafts. At 3 and 6 months postoperatively, the signal intensity of the tunnel walls was decreased significantly, while that of the intraosseous tendon grafts was also decreased, but not significantly. At these times, the SNRs of the femoral and tibial tunnels did not differ significantly, both overall and in the region of the intraosseous tendon grafts. CONCLUSION: Revascularization around the femoral and tibial tunnels occurred at 2 months postoperatively, with blood flow subsequently decreasing over time until 6 months. This revascularization may be involved in bone tendon healing and maturation of the tendon graft within the bone tunnels. Evaluations of revascularization by MRA may show the maturation stage of the graft and guide medical rehabilitation. LEVEL OF EVIDENCE: IV.

Comparison of Alignment Correction Angles Between Fixed-Bearing and Mobile-Bearing UKA.

Good outcomes have been reported with both fixed-bearing and mobile-bearing unicompartmental knee arthroplasty (UKA). However, overcorrected alignment could induce the progression of arthritis on the non-arthroplasty side. Changes of limb alignment after UKA with both types of bearings (fixed bearing: 24 knees, mobile bearing: 28 knees) were investigated. The mean difference between the preoperative standing femoral-tibial angle (FTA) and postoperative standing FTA was significantly larger in mobile bearing UKA group. In fixed-bearing UKA, there must be some laxity in MCL tension so that a 2-mm tension gauge can be inserted. In mobile-bearing UKA, appropriate MCL tension is needed to prevent bearing dislocation. This difference in MCL tension may have caused the difference in the correction angle between the groups.

Quantitative evaluation of revascularization at bone tunnels and grafts with contrast-enhanced magnetic resonance angiography after anterior cruciate ligament reconstruction.

PURPOSE: Quantitative evaluation of vascular ingrowth to the bone tunnel walls and tendon graft after anterior cruciate ligament reconstruction for up to two years post-surgery using magnetic resonance angiography (MRA). METHODS: The study population consists of 100 patients that underwent reconstruction with multi-stranded semitendinosus tendons. The patients were retrospectively divided into those that underwent MRA two, three, four to six, and ≥ seven months after surgery (46, 17, 16, and 21 patients, respectively). Digital imaging and communication in medicine (DICOM) MRA images were imported into image processing software (OsiriX®), and the mean signal-to-noise ratio (SNR) of the bone tunnel walls in the femur and tibia and tendon graft parenchyma in the bone tunnels were measured. RESULTS: On MRA, the signal intensities of the bone tunnel walls in the femur and tibia (12.6 ± 3.41 and 10.7 ± 3.04) were greater than that in the tendon graft (2.65 ± 1.94 and 2.50 ± 2.02, respectively) at two months after surgery. At three months after surgery, the intensities of the tendon grafts (6.25 ± 2.18 and 5.77 ± 1.57, respectively) were greater than those of the bone tunnel wall (2.56 ± 1.29 and 2.50 ± 1.11, respectively). At four to six months, the intensities in the bone tunnel wall were 1.76 ± 0.73 and 1.62 ± 0.72, respectively, and those in the tendon graft were 5.01 ± 2.11 and 4.01 ± 2.35, respectively. At ≥ seven months after surgery, the intensities in the bone tunnel wall were 1.36 ± 0.63 and 1.21 ± 0.87, respectively, and those in the tendon graft were 4.25 ± 1.87 and 3.44 ± 1.99, respectively. CONCLUSION: Blood flow was seen around the bone tunnel on the femoral and tibial sides two months after ACL reconstruction and in the tendon graft parenchyma three months after surgery. The remodeling process continued after seven months.

Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage.

Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses.

Factors affecting range of motion after total knee arthroplasty in patients with more than 120 degrees of preoperative flexion angle.

PURPOSE: The postoperative flexion angle reportedly shows a positive correlation with the preoperative flexion angle, but in some cases, the postoperative flexion angle decreases in patients with a large preoperative flexion angle. The purpose of this study was to investigate factors affecting the range of motion after total knee arthroplasty (TKA) in patients with a large preoperative flexion angle. METHODS: The study evaluated 120 knees with more than 120 degrees of preoperative flexion angle that underwent NexGen LPS-Flex mobile bearing. The groups with and without a reduction in the postoperative flexion angle were compared. Also, a logistic regression analysis was performed, where the presence or absence of a reduction in the postoperative flexion angle was the dependent variable and age, sex, body mass index (BMI), preoperative femorotibial angle (FTA), γ angle, δ angle, pre/postoperative change amount in posterior condylar offset (PCO), pre/postoperative change amount in joint line, and pre/postoperative change amount in patellar thickness were independent variables. RESULTS: Those with preoperative FTA of 186° or larger did not have a reduction in the postoperative flexion angle, compared with the angle of 185° or smaller. Those with δ angle of 83° or smaller also did not have a reduction in the postoperative flexion angle, compared with the angle of 84° or larger. CONCLUSIONS: Our results showed that preoperative FTA and δ angle had an impact on a reduction in the postoperative flexion angle. The installation angle of the tibial component in the sagittal plane is important.

Characteristics of medial plica syndrome complicated with cartilage damage.

PURPOSE: This study was designed to evaluate the characteristics of patients with medial plica syndrome and associated cartilage damage. METHODS: The study subjects included 44 patients with 57 knees arthroscopically diagnosed with medial plica syndrome. Subjects were divided into those with severe cartilage damage, defined as International Cartilage Research Society (ICRS) stage 2 or higher, and those with mild cartilage damage, defined as ICRS stage 1 or lower. Local findings, period from onset to surgery, arthroscopic findings, and postoperative results were compared in the two groups. RESULTS: The shapes of the medial synovial plica were types C and D of the Sakakibara classification in the severe group, and types A, B, and C in the mild group. Patellar ballottement tended to be more common in the severe than in the mild group (P = 0.059). The duration from onset to surgery was significantly longer in the severe than in the mild group (29.0 vs. 11.6 months, P = 0.043). Postoperative results were significantly better in the mild than in the severe group (P = 0.0017). CONCLUSIONS: The shape of the medial synovial plica and the duration between symptom onset and surgery were associated with cartilage damage. Surgical treatment should be considered when the medial synovial plica covers part of the anterior aspect of the medial femoral condyle or ruptures, or when pain persists over a long period, thus reducing the potential for cartilage damage. LEVEL OF EVIDENCE: Level IV.

Hydrostatic pressure influences HIF-2 alpha expression in chondrocytes.

Hypoxia-inducible factor (HIF)-2α is considered to play a major role in the progression of osteoarthritis. Recently, it was reported that pressure amplitude influences HIF-2α expression in murine endothelial cells. We examined whether hydrostatic pressure is involved in expression of HIF-2α in articular chondrocytes. Chondrocytes were cultured and stimulated by inflammation or hydrostatic pressure of 0, 5, 10, or 50 MPa. After stimulation, heat shock protein (HSP) 70, HIF-2α, nuclear factor kappa B (NF-κB), matrix metalloproteinase (MMP)-13, MMP-3, and vascular endothelial growth factor (VEGF) gene expression were evaluated. The levels of all gene expression were increased by inflammatory stress. When chondrocytes were exposed to a hydrostatic pressure of 5 MPa, HIF-2α, MMP-13, and MMP-3 gene expression increased significantly although those of HSP70 and NF-κB were not significantly different from the control group. In contrast, HIF-2α gene expression did not increase under a hydrostatic pressure of 50 MPa although HSP70 and NF-κB expression increased significantly compared to control. We considered that hydrostatic pressure of 5 MPa could regulate HIF-2α independent of NF-κB, because the level of HIF-2α gene expression increased significantly without upregulation of NF-κB expression at 5 MPa. Hydrostatic pressure may influence cartilage degeneration, inducing MMP-13 and MMP-3 expression through HIF-2α.