Foot orthosis treatment improves physical activity but not muscle quantity in patients with concurrent rheumatoid arthritis and sarcopenia.

OBJECTIVES: Foot impairment in rheumatoid arthritis (RA) may exacerbate sarcopenia from physical inactivity because of foot pain while walking. The present study aimed to investigate the prevalence of sarcopenia in patients with RA-associated foot impairment, and whether treatment with a foot orthosis improved physical activity and muscle quantity. METHODS: Thirty-two patients with RA were diagnosed as sarcopenic or nonsarcopenic, and the prevalence of sarcopenia was determined. Eleven patients with sarcopenia were treated with a foot orthosis. The following parameters were compared between baseline and after 6 months of treatment: physical activity (walking, moderate-intensity activity, and vigorous-intensity activity), foot pain while walking, Health Assessment Questionnaire (HAQ) score, and body composition parameters, including muscle quantity. RESULTS: Sarcopenia was present in 25/32 patients (78.1%). The use of a foot orthosis improved walking activity (p = .02), foot pain while walking (p = .02), and HAQ score (p = .02). However, there were no significant changes in moderate- or vigorous-intensity activities or body composition parameters, including muscle quantity. CONCLUSION: Patients with RA-associated foot impairment had a high rate of sarcopenia. Treatment with a foot orthosis increases light-intensity physical activity such as walking, but does not enhance moderate-to-vigorous-intensity activities or increase muscle quantity.

A new assessment tool for ulnar drift in patients with rheumatoid arthritis using pathophysiological parameters of the metacarpophalangeal joint.

OBJECTIVES: To establish a new assessment tool for ulnar drift (UD) in rheumatoid arthritis (RA). METHODS: We established an observational cohort of 67 patients (134 rheumatoid hands) beginning in 2004. Fifty-two patients (100 hands) had follow-up in 2009 and 37 patients (63 hands) completed follow-up in 2015. UD was evaluated with the Fearnley classification and our scoring method, which assesses four parameters of the metacarpophalangeal joint. Cluster analysis using UD parameters divided hands into groups. Changes in UD over time, correlation of the Fearnley stage and cluster with a functional assessment, and reliability of the parameters were analyzed. RESULTS: UD increased and worsened over time according to the trend test. A dendrogram indicated five clusters would be appropriate. Both the Fearnley classification and cluster were associated with function; however, our method related to function more linearly (R-squared: 0.42). We found one type of hand in which bone destruction precedes the joint dislocation and one type in which joint dislocation progresses with little deviation during UD progression. CONCLUSION: Our UD evaluation appeared to be simple and related to function. Additionally, it enables dividing UD hands into five stages. Thus, our assessment should be beneficial compared to the Fearnley classification in considering treatments of UD.

Recurrence of deformity after silicone implant and resection arthroplasty of the metatarsophalangeal joint for rheumatoid arthritis: long-term results.

OBJECTIVE: To examine the recurrence of deformity after silicone implant arthroplasty combined with resection arthroplasty for severe forefoot deformity in patients with rheumatoid arthritis. METHODS: We reviewed the long-term results of this procedure for 27 feet in 15 patients. Their average age and disease duration at the time of operation were 58.6 years and 17.5 years, respectively, and the average follow-up period was 10.3 years. RESULTS: An improved hallux valgus angle (45.3° preoperatively, 23.6° 6 months after operation) was maintained. By contrast, deformity and dislocation of lesser toe had recurred at the final follow-up; the angle between the proximal phalanx and the metatarsal of the second toe improved 13.4° with recurrence of 22.5°, the angle between the proximal phalanx and ground surface improved 22.4° with recurrence of 34.5. Furthermore, claw toe deformity at the final follow-up was significantly worse in the group whose hallux valgus deformity was observed 6 months after operation. CONCLUSION: This procedure could maintain the alignment of the first metatarsophalangeal joint, but the recurrence of claw toe deformity is a problem and the relation between the first toe and the lesser toe is an important consideration.

Weight-bearing three-dimensional computed tomography analysis of the forefoot in patients with flatfoot deformity.

BACKGROUND: The recent classifications for posterior tibial tendon dysfunction (PTTD) stage II are based on forefoot deformity, but there is still no consensus regarding a detailed explanation of the clinical condition. The purposes of this study were to clarify the clinical condition of flatfoot deformity using three-dimensional (3D) computed tomography (CT) imaging under loading on both healthy and flat feet and to compare 3D movement of the forefoot in response to load. METHODS: Ten volunteers and 10 PTTD stage II patients with symptomatic flatfoot deformity were examined. CT scans of 20 healthy and 20 flat feet were performed under non-loading and full weight-bearing conditions. Images of the tibia and foot arch bones (talus, calcaneus, navicular, and first and fifth metatarsal bones) were reconstructed into 3D models. Rotations of individual tarsal bone or metatarsal bone were described by the Eulerian angles. RESULTS: Compared with healthy feet, flat feet experienced plantarflexion of the fifth metatarsal bone relative to the first metatarsal bone under loading conditions. We defined this phenomenon as synonymous with forefoot varus on the coronal plane. CONCLUSIONS: The results of this study have clarified part of the clinical condition of the forefoot in flatfoot deformity and may have applications in basic research of the staging advancement and substage classification of PTTD.

Spontaneous flexor tendon rupture in systemic lupus erythematosus: A case report.

Spontaneous flexor tendon rupture is an unusual complication of systemic lupus erythematosus (SLE) and has not previously been reported. While tendon ruptures in association with SLE have been focused on the previous studies, upper extremity tendon ruptures are infrequently reported in the literature. Here, we present an uncommon case of spontaneous flexor tendon rupture of the ring and little fingers in a patient with SLE and discuss the mechanism of injury and its surgical treatment.

Rheumatoid arthritis of the hand: a five-year longitudinal analysis of clinical and radiographic findings.

OBJECTIVES: Treatments for rheumatoid arthritis (RA) have improved since methotrexate and biological agents were approved; however, few longitudinal analyses have tracked joint destruction, deformity progression, or functional impairments that directly affect the activities of daily living. Due to the consequences of functional impairments, we conducted this study to glean more information regarding deformity progression over time. METHODS: This study enrolled 134 hands in 67 RA patients with hand deformities in 2004. After 5 years, 100 hands in 52 patients were eligible for the final assessment. Analyses consisted of morphological and radiographical evaluations of deformities, functional evaluations by questionnaires and the modified Kapandji index, and activity evaluations. RESULTS: In this period, the type I deformity (Nalebuff and Millender, Orthop Clin North Am 6(3):753-63, 1975) was the most common thumb deformity. Swan-neck and boutonnière finger deformities also progressed. At the 5-year follow-up, questionnaire score worsened, when disease activity was high. CONCLUSIONS: Our study showed that there was a marked progression in hand deformities in RA patients over a 5-year period. In order to assist RA patients in performing the activities of daily living, medical and rehabilitative interventions should target the restoration of functional loss through joint destruction as well as the prevention of disease progression.

Spontaneous tendon rupture of the extensor digitrum communis in systemic lupus erythematosus.

We present a rare case of spontaneous tendon rupture of the extensor digitorum communis (EDC) in a patient with systemic lupus erythematosus (SLE). Inflammation in SLE presents as periarthritis, which may develop into Jaccoud's arthropathy. We bridged the ruptured tendon of the EDC (III) at the metacarpophalangeal (MP) joint of this patient with a tendon graft. This case demonstrates that this portion of the MP joint can be a site of tendon rupture of fingers in SLE patients.

Effect of Foot Orthosis Treatment on Quality of Life in Secondary Sarcopenia Patients with Rheumatoid Arthritis-Related Foot Impairment.

Objectives: Patients with rheumatoid arthritis (RA)-related foot impairment have a high rate of sarcopenia. Treatment using a foot orthosis (FO) enables not only a reduction in pain while walking but also an increase in physical activity, helping to prevent further loss of muscle mass. However, the primary goal of treating RA is to maximize patients' long-term quality of life (QOL). We investigated whether FO treatment both increases physical activity and improves QOL. Methods: Among 31 patients with RA-related foot impairment, 15 with sarcopenia were treated with an FO for 6 months. Foot-specific QOL (measuring using the Self-Administered Foot Evaluation Questionnaire), foot pain, activities of daily living, and physical activity (walking-intensity activity and moderate- to vigorous-intensity activity) were compared before treatment and after 6 months of treatment. Results: Ten patients who completed 6 months of follow-up were analyzed. Significant QOL improvements were found in the Pain and Pain-Related category and the Physical Functioning and Daily Living category (P = 0.02-0.04); however, no significant changes were found in the Social Functioning, General Health and Well-Being, or Shoe-Related categories (P = 0.09-0.21). Foot pain and activities of daily living significantly improved (P = 0.01-0.04). Physical activity significantly increased for walking-intensity activity (P = 0.04) but did not change for moderate- to vigorous-intensity activity (P = 1.00). Conclusions: FO treatment in patients with RA-related foot impairment and sarcopenia increased light-intensity physical activity such as walking and improved physical QOL.

Features of hindfoot 3D kinetics in flat foot in ankle-joint maximal dorsiflexion and plantarflexion.

BACKGROUND: It is difficult to evaluate the kinematics of flat foot from 2D images, and no definitive methods have so far been established to diagnose flat foot. This study evaluated hindfoot kinetics through the progression of posterior tibial tendon dysfunction (PTTD) in patients with stages II and III PTTD flat foot compared with those in normal patients under dorsiflexion and plantarflexion conditions using 3D computed tomography (CT) reconstruction images. MATERIALS: CT images were taken of 26 normal and 32 flat feet in neutral, plantarflexion, and dorsiflexion positions of the ankle joint, from which 3D virtual models were made of each hindfoot bone. The 3D bone motion of these models was calculated using volume merge methods in three major planes. RESULTS: Tibiotalar-joint motion in ankle-joint plantarflexion became less plantarflexed (normal -41.2°, stage II -33.5°, stage III -25.3°) and less adducted (normal -13.9°, stage II -10.7°, stage III -5.6°) as the stage progressed. Talocalcaneal-joint motion in stage III became more plantarflexed (normal -0.8°, stage II -3.0°, stage III -8.7°) and more adducted (normal -0.3°, stage II -4.7°, stage III -10.3°) as the stage progressed. Talonavicular-joint motion in stage III became more plantarflexed (normal -7.2°, stage II -7.6°, stage III -14.9°) and more adducted (normal 1.0°, stage II -7.3°, stage III -17.9°) as the stage progressed. CONCLUSIONS: Tibiotalar-joint plantarflexion decreased and talocalcaneal and talonavicular-joint adduction increased in the maximal ankle-joint plantarflexion in stage II in comparison with normal cases. Tibiotalar-joint plantarflexion and adduction were decreased and of the talocalcaneal and talonavicular joints increased in stage III in comparison with stage II cases.

Load response of the tarsal bones in patients with flatfoot deformity: in vivo 3D study.

BACKGROUND: The objective of this study was to evaluate the bone rotation of each joint in the hindfoot and compare the load response in healthy feet with that in flatfeet by analyzing the reconstructive three-dimensional (3D) CT image data during weightbearing. METHODS: CT scans of 21 healthy feet and 21 feet with flatfoot deformity were taken in non-load condition followed by full-body weightbearing load condition. The images of the hindfoot bones were reconstructed into 3D models. The volume merge method in three planes was used to calculate the position of the talus relative to the tibia in the tibiotalar joint, the navicular relative to the talus in talonavicular joint, and the calcaneus relative to the talus in the talocalcaneal joint. RESULTS: The talar position difference to the load response relative to the tibia in the tibiotalar joint in a flatfoot was 1.7 degrees more plantarflexed in comparison to that in a healthy foot (p = 0.031). The navicular position difference to the load response relative to the talus in the talonavicular joint was 2.3 degrees more everted (p = 0.0034). The calcaneal position difference to the load response relative to the talus in the talocalcaneal joint was 1.1 degrees more dorsiflexed (p = 0.0060) and 1.7 degrees more everted (p = 0.0018). CONCLUSION: Referring to previous cadaver study, regarding not only the cadaveric foot, but also the live foot, joint instability occurred in the hindfoot with load in patients with flatfoot. CLINICAL RELEVANCE: The method used in this study might be applied to clinical analysis of foot diseases such as the staging of flatfoot and to biomechanical analysis to evaluate the effects of foot surgery in the future.

Comprehensive assessment of alterations in hand deformities over 11 years in patients with rheumatoid arthritis using cluster analysis and analysis of covariance.

BACKGROUND: Although drug therapy for rheumatoid arthritis (RA) has recently improved, treating patients with established disease, whose hands have three major deformities (thumb deformity, finger deformities, and ulnar drift), remains a challenge. The underlying complex pathophysiology makes understanding these deformities difficult, and comprehensive assessment methods require accumulated skill with long learning curves. We aimed to establish a simpler composite method to understand the pathophysiology of and alterations in the hand deformities of patients with RA. METHODS: We established a rheumatoid hand cohort in 2004 and clinically evaluated 134 hands (67 patients). We repeated the evaluations in 2009 (100 hands of 52 patients) and 2015 (63 hands of 37 patients) after case exclusion. Thumb deformities, finger deformities (swan-neck and boutonnière deformity), and ulnar drift were semi-quantitated and entered as parameters into a two-step cross-sectional cluster analysis for the data in 2004. The parameters in each cluster were plotted at each evaluation point. Two-way analysis of covariance was used to examine whether differences existed between evaluation points and clusters of deformity parameters. RESULTS: Five clusters most appropriately described hand deformity: (i) cluster 1, minimal deformity; (ii) cluster 2, type 1 thumb deformity; (iii) cluster 3, thumb deformity and severe boutonnière deformity; (iv) cluster 4, type 2 or 3 thumb deformity and severe ulnar drift; and (v) cluster 5, thumb deformity and severe swan-neck deformity. Clusters 1 and 2 had higher function than cluster 5, and cluster 3 had moderate function. Clusters 1-4 had similar disease duration but showed different paths of deformity progression from disease onset. Clusters 1 and 2 represented conservative deformity parameters and clusters 3, 4, and 5 represented progressive deformity parameters. Over time, thumb deformity evolved into other types of deformities and swan-neck deformity worsened significantly. CONCLUSIONS: Our comprehensive analysis identified five deformity patterns and a progressive course in the rheumatoid hand. Knowledge of the characteristics of progressive deformity parameters may allow rheumatologists to more easily implement practical interventions and determine functional prognosis.

MDR1a/1b gene silencing enhances drug sensitivity in rat fibroblast-like synoviocytes.

BACKGROUND: Drug resistance mediated by P-glycoprotein (P-gp) is one of the major reasons for the failure of rheumatoid arthritis (RA) therapy with disease modifying anti-rheumatic drugs and glucocorticoids. In the present study, we aimed to investigate the in vitro effectiveness of small interfering RNA (siRNA) to render rat fibroblast-like synoviocytes (FLS) susceptible to drugs. We also attempted the electroporation-mediated transfer of siRNA against multidrug resistance (MDR) genes into rat knee joints. METHODS: FLS were transfected with siRNAs corresponding to MDR1a and MDR1b genes. FLS were treated with dexamethasone (DEX) and lipopolysaccharide. The mRNA and protein levels of tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1beta were measured. Both siRNAs were co-transduced into rat knee joints by an electroporation method and evaluated the target gene expressions in the synovium. RESULTS: Each siRNA could sequence-specifically reduce the target gene expression by over 70% and effectively suppressed P-gp expression and function in the FLS. Both gene expression and protein production of the inflammatory cytokines in the cells transfected with siRNA were reduced by a greater amount compared to in control cells. The in vivo electroporation-mediated transduction of siRNA could significantly inhibit the target gene expressions. CONCLUSIONS: MDR1a/1b gene silencing by siRNA could effectively inhibit P-gp in rat FLS, resulting in a significant enhancement of the anti-inflammatory effects of DEX. The in vivo siRNA transduction could successfully silence MDR gene expression in the rat synovium. These findings indicate that the siRNA targeting MDR gene could be a useful tool for treating refractory arthritis in RA.

An analysis of the medial patellofemoral ligament length change pattern using open-MRI.

Recently, for a recurrent patellar dislocation, medial patellofemoral ligament (MPFL) reconstruction has come to be commonly performed, yet the precise in vivo MPFL biomechanics still remains to be clarified. The purpose of this study was to analyze the length change pattern of MPFL in vivo. The subjects were comprised of ten male and ten female healthy volunteers. The length of the MPFL was measured using an open-MRI both from a leg extended position and a highly knee-flexed position in order to analyze the length change pattern of the MPFL. The MPFL length for men and women resulted in an average of 52 ± 3 mm and 43 ± 2 mm at the knee extended position, respectively. The length change pattern of the MPFL presented a slight change at up to a flexion angle of 60° and a decrease at over 60°. In terms of morphology, the fiber bundle of the MPFL experienced linear tension at a knee flexion angle of 60°. We determined that the MPFL length in vivo exhibited a specific length change pattern. MPFL mainly contributes to the medial constraint of a patella with a knee flexion of 0° to 60°, wherein it is expected to have the strongest strain at 60°. However, more studies are needed to obtain a better understanding of cases with a history of patellar dislocation.

A modified Terrono classification for Type 1 thumb deformity in rheumatoid arthritis: a cross-sectional analysis.

The most common thumb deformity in rheumatoid arthritis is Nalebuff Type 1 deformity (boutonniere deformity). Type 1 deformity severely impairs hand function, and this impairment is evaluated by the Terrono classification. In some cases, the Terrono classification incorrectly categorizes advanced thumb deformity into earlier stages. We modified the Terrono classification by assessing the active range of motion of the interphalangeal joint prior to assessing the passive range of movement of the metacarpophalangeal joint. An active range of movement of the interphalangeal joint was strongly correlated with hand function. In 55 hands that we treated between 2004 and 2015, we compared the modified classification with the original Terrono classification. Our modified classification could detect advanced deformity earlier, and was more strongly correlated with hand function. Additionally, correlation analysis showed that advanced Type 1 deformity should be treated first, even in cases with severe ulnar drift. Our results suggest that the modified classification may benefit the treatment of Type 1 deformity, including joint-preserving surgery. Level of evidence: III.

In vivo three-dimensional analysis of hindfoot kinematics.

BACKGROUND: Knowledge of normal bone motion of the foot is important for understanding the gait as well as for various pathologies; however, the pattern of 3D motion is not completely understood. The aim of this study was to quantify the in vivo motion of the tibiotalar joint, talocalcaneal joint, and talonavicular joint in normal adult feet using a noninvasive (e.g., nonsurgical) measurement technique. MATERIALS AND METHODS: CT images were taken of both feet of ten normal young adults (six males, four females) in neutral, plantarflexion, and dorsiflexion positions of the ankle joint, from which 3D virtual models were made of each mid-hind foot bones. The 3D bone motion of these models was calculated using volume merge methods in three major planes. These data were used to analyze the relationship between the motion of the ankle joint and each other joint. RESULTS: Tibiotalar rotation was observed in dorsiflexion, abduction, and eversion during maximal dorsiflexion of the ankle joint. Talocalcaneal and talonavicular rotation was very small because the ankle joint motion was limited to the sagittal plane. Tibiotalar rotation was also observed in plantarflexion and adduction during maximal plantarflexion of the ankle joint, and talocalcaneal rotation was very small. Talonavicular rotation was observed in plantarflexion and inversion. The motion of the x-axis and the z-axis of tibiotalar joint, and the x-axis and the y-axis of the talonavicular and talocalcaneal joint were associated with the ankle motion. CONCLUSION: Bone motion could be easily and accurately calculated using volume merge methods more effectively than it could with other methods. CLINICAL RELEVANCE: The data elucidates the baseline segmental motion for comparison with symptomatic subjects which could help us to better understand pathokinematics of various foot and ankle pathologies.

Degeneration of the Sacroiliac Joint in Hip Osteoarthritis Patients: A Three-Dimensional Image Analysis.

OBJECTIVE: The sacroiliac joint is an important source of low back pain and may be influenced by pathologies in adjoining structures such as the hip or the spine. This study aimed to investigate the influence of hip osteoarthritis on sacroiliac joint degeneration by examining the sacroiliac joints of hip osteoarthritis patients, focusing on the localization and quantity of vacuum phenomena. MATERIALS AND METHODS: The preoperative computed tomography (CT) of 31 female hip replacement candidates (mean age 69.1) and pelvic CT of 34 age-matched controls (mean age 67.9) were used to reconstruct the sacroiliac joints three-dimensionally. The degeneration score of the sacroiliac joints on axial view, as well as the location and volume of vacuum phenomena in the three-dimensionally reconstructed sacroiliac joints, were analyzed. RESULTS: The total sacroiliac joint degeneration scores were similar in hip osteoarthritis patients and controls but the breakdown of the score revealed that joint space narrowing and vacuum phenomena in the sacroiliac joint increase in hip osteoarthritis, while osteophytes decrease. Three-dimensional reconstruction revealed that the volume of vacuum phenomena in the sacroiliac joint was significantly larger in the hip osteoarthritis group and the vacuum areas were localized in the antero-superior region of the sacroiliac joint. CONCLUSION: Our results suggest that hip osteoarthritis and sacroiliac joint degeneration are related, and that with further investigation, the sacroiliac joint may become a new treatment target in hip osteoarthritis.

Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis.

Mycoplasma fermentans has been suspected as one of the causative pathogenic microorganisms of rheumatoid arthritis (RA) however, the pathogenic mechanism is still unclear. We, previously, reported that glycolipid-antigens (GGPL-I and III) are the major antigens of M. fermentans. Monoclonal antibody against the GGPL-III could detect the existence of the GGPL-III antigens in synovial tissues from RA patients. GGPL-III antigens were detected in 38.1% (32/84) of RA patient's tissues, but not in osteoarthritis (OA) and normal synovial tissues. Immunoelectron microscopy revealed that a part of GGPL-III antigens are located at endoplasmic reticulum. GGPL-III significantly induced TNF-alpha and IL-6 production from peripheral blood mononulear cells, and also proliferation of synovial fibroblasts. Further study is necessary to prove that M. fermentans is a causative microorganism of RA; however, the new mechanisms of disease pathogenesis provides hope for the development of effective and safe immunotherapeutic strategies based on the lipid-antigen, GGPL-III, in the near future.

Evaluation of lateral instability of the atlanto-axial joint in rheumatoid arthritis using dynamic open-mouth view radiographs.

Upper cervical involvement is common in patients with rheumatoid arthritis (RA). Anterior atlanto-axial subluxation (aAAS) sometimes occurs at an early stage of the disease. We hypothesized that not only antero-posterior instability but lateral instability may occur with atlanto-axial involvement in RA. To prove this hypothesis, we evaluated the lateral instability of the atlanto-axial joint in RA, using dynamic open-mouth view radiographs. Thirty RA patients and a control group of 22 non-RA outpatients were enrolled in this study. The patients underwent lateral view radiographs of the cervical spine during flexion and extension, and antero-posterior (AP) open-mouth views during maximum right and left bending of the neck. The anterior atlanto-dental interval (AADI) was measured to evaluate antero-posterior instability of the atlanto-axial joint, and atlanto-dental lateral shift (ADLS) was defined to evaluate dynamic lateral instability. In the RA group, AADI averaged 3.2 mm in flexion, and in eight patients, it exceeded 3 mm in flexion (aAAS). In the control group, the AADI averaged 1.0 mm in flexion. The ADLS in the RA group averaged 14.8%, and this was significantly greater than in the control group, in which it averaged 6.1%. The ADLS averaged 20.6% in the RA subgroup with aAAS, and 12.7% in the RA subgroup without aAAS. In both subgroups, the ADLS was significantly greater than that of the control group. In this study, dynamic lateral instability of the atlanto-axial joint in RA was demonstrated. The results suggest that an evaluation of the dynamic lateral instability of the atlanto-axial joint can be useful for early diagnosis of atlanto-axial lesions in RA.

Behavior of host and graft cells in the early remodeling process of rotator cuff defects in a transgenic animal model.

Autologous tissue graft is one of the treatment options for a large rotator cuff defect. To develop appropriate strategies for enhanced solid graft integration at the bone-tendon interface and tendon-tendon interface, clarifying the fate of the graft and host cells that contribute to repair and remodeling is necessary. We have developed a new grafting model using green fluorescent protein-transgenic rats and wild-type rats to simulate autologous transplantation for examining the behavior of the host and graft cells in the remodeling process after tendon grafting. We found that the host cells commenced proliferation in the graft at 1 day after grafting. The host cells infiltrated into the graft from the subacromial synovium, proximal tendon, and bone-tendon insertion. The number of graft-derived cells decreased with time. Our result clearly demonstrated that host cells, rather than graft cells, were essential for rotator cuff remodeling after tendon grafting for rotator cuff defect.

Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Delta-Prostaglandin J(2).

15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-gamma ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ(2) can suppress interleukin (IL)-1beta-induced prostaglandin E(2) (PGE(2)) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE(2) synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ(2) led to a significant increase in IL-1alpha-induced COX-2 expression and PGE(2) production in a dose dependent manner. The effect of 15d-PGJ(2) was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ(2) exerts a positive feedback regulation of the arachidonate cascade of PGE(2) in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis.