Effects of metformin on knee joint capsule fibrosis in a diabetic mouse model.

Aims: The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Methods: Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro. Results: The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (Ccn2) in WT mouse cells. Conclusion: Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis.

Effects of differences in dose and frequency of teriparatide on bone structure in Proximal Femur. - Analysis by DXA-based 3D-modeling (3D-SHAPER Software) -TRIPLE-BONE study (The effects of TeRIParatide preparation on bone mineraL density increase and BONE structure).

Trends toward more favorable improvement of the cortical bone parameters by once-weekly (56.5 µg once a week) and twice-weekly teriparatide (28.2 µg twice a week), and that of the trabecular bone parameters by once-daily (1/D) teriparatide (20 µg/day once a day) were shown. PURPOSE: To examine the effects of differences in the amount of teriparatide (TPTD) per administration and its dosing frequency on the bone structure in the proximal femur by dual-energy X-ray absorptiometry (DXA)-based 3D-modeling (3D-SHAPER software). METHODS: This was a multicenter retrospective study. Patients aged 50 years or older with primary osteoporosis who continuously received once-/twice-weekly (1・2/W, n = 60) or 1/D TPTD (n = 14) administration for at least one year were included in the study. Measurement regions included the femoral neck (FN), trochanter (TR), femoral shaft (FS), and total proximal hip (TH). Concurrently, the bone mineral density (BMD) and Trabecular Bone Score (TBS) were measured. RESULTS: The cross-sectional area, cross-sectional moment of inertia, and section modulus in the FS were significantly improved in the 1・2/W TPTD group, as compared to the 1/D TPTD group. However, significant improvement of the cortical thickness and buckling ratio in the FN was observed in the 1/D TPTD group, as compared to the 1・2/W TPTD group. Trabecular BMD values in the FS and TH were significantly increased in the 1/D TPTD group, as compared to the 1・2/W TPTD group, while the cortical BMD values in the TR, FS, and TH were significantly increased in the 1・2/W TPTD group, as compared to the 1/D TPTD group. CONCLUSION: Trends toward more favorable improvement of the cortical bone by 1・2/W TPTD and that of the trabecular bones by 1/D TPTD were observed.

Clinical Outcomes and Return-to-Sport Rates following Fragment Fixation Using Hydroxyapatite/Poly-L-Lactate Acid Threaded Pins for Knee Osteochondritis Dissecans: A Case Series.

Osteochondritis dissecans (OCD) of the knee is an uncommon injury in young active patients. There is currently a lack of knowledge regarding clinical outcomes and return-to-sport rates after fragment fixation surgery using hydroxy appetite poly-L-lactic acid (HA/PLLA) threaded pins for knee OCD among athletes. Our purpose was to investigate the clinical outcomes and return-to-sport rates following osteochondral fragment fixation using HA/PLLA pins for the treatment of knee OCD lesions among athletes. A total of 45 patients were retrospectively reviewed. In total, 31 patients were excluded, and 14 patients were included. Pre- and postoperative patient-reported outcome scores (PROSs), including the International Knee Documentation Committee (IKDC) score and Knee Injury and Osteoarthritis Outcome Scale (KOOS), were compared. In addition, patients were categorized into four groups according to postoperative sports status: higher, same, lower than preinjury, or unable to return to sports. The mean age was 14.4 years (SD 1.67). All patients were male. All PROSs significantly improved at 6, 12, and 24 months postsurgery compared to presurgery. 50% of the patients returned to sports at the same or higher level after surgery. Fragment fixation using HA/PLLA pins leads to favorable clinical outcome scores and high return-to-sport rates in the treatment of athletes with knee OCD.

The impact of chronic obstructive pulmonary disease on bone strength.

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties.

Nitric oxide synthase contributes to the maintenance of LTP in the oxytocin-mRFP1 neuron of the rat hypothalamus.

Oxytocin (OXT) is a neuropeptide hormone that plays a critical role in nociception. Long-term potentiation (LTP) is a major form of synaptic plasticity in the central nervous system. Recently, LTP has been reported in the hypothalamus; however, data on LTP in hypothalamic OXT-ergic neurons are unclear. Furthermore, the signaling pathways for hypothalamic OXT-ergic neuronal LTP and its physiological significance remain unknown. Herein, we aimed to investigate the induction of hypothalamic OXT-ergic neuronal LTP and its synaptic mechanism using OXT-monomeric red fluorescent protein 1 transgenic rats to visualize and record from OXT-ergic neurons. The hypothalamic paraventricular nucleus (PVN) OXT-ergic neuronal LTP induced by the pairing protocol was dependent on N-methyl-D-aspartate receptor (NMDAR). Furthermore, nitric oxide synthase (NOS) is required to maintain the LTP regardless of the NMDARs. In addition, hypothalamic OXT-ergic neuronal LTP was not induced in the adjuvant arthritis rat model but increased excitatory postsynaptic currents were detected. LTP in hypothalamic OXT-ergic neurons in the PVN in the presence of NOS may be involved in neuronal changes during OXT synthesis in chronic inflammation.

Adiponectin inhibits fibrosis of the palmar aponeurosis in Dupuytren's contracture in male patients.

Aims: Dupuytren's contracture is characterized by increased fibrosis of the palmar aponeurosis, with eventual replacement of the surrounding fatty tissue with palmar fascial fibromatosis. We hypothesized that adipocytokines produced by adipose tissue in contact with the palmar aponeurosis might promote fibrosis of the palmar aponeurosis. Methods: We compared the expression of the adipocytokines adiponectin and leptin in the adipose tissue surrounding the palmar aponeurosis of male patients with Dupuytren's contracture, and of male patients with carpal tunnel syndrome (CTS) as the control group. We also examined the effects of adiponectin on fibrosis-related genes and proteins expressed by fibroblasts in the palmar aponeurosis of patients with Dupuytren's contracture. Results: Adiponectin expression in the adipose tissue surrounding the palmar aponeurosis was significantly lower in patients with Dupuytren's contracture than in those with CTS. The expression of fibrosis-related genes and proteins, such as types 1 and 3 collagen and α-smooth muscle actin, was suppressed in a concentration-dependent manner by adding AdipoRon, an adiponectin receptor agonist. The expression of fibrosis-related genes and proteins was also suppressed by AdipoRon in the in vitro model of Dupuytren's contracture created by adding TGF-ß to normal fibroblasts collected from patients with CTS. Conclusion: Fibrosis of the palmar aponeurosis in Dupuytren's contracture in males may be associated with adiponectin expression in the adipose tissue surrounding the palmar aponeurosis. Although fibroblasts within the palmar aponeurosis are often the focus of attention when elucidating the pathogenesis of Dupuytren's contracture, adiponectin expression in adipose tissues warrants closer attention in future research.

Validity and application of Doiguchi's pelvic tilt measurement method.

BACKGROUND: The validity of Doiguchi's pelvic tilt measurement method has not been proven. The objective in our study was to validate the method. METHODS: Our investigation included 73 total hip arthroplasties (THAs) performed using our cup placement procedure from July 2020 to November 2021. Pelvic tilt formed by the pubic symphysis and sacral promontory (PTPS) in supine and lateral positions was calculated by two methods (the Doiguchi method and the digital reconstructed radiograph (DRR) method using a 3D computer templating system) based on the transverse and longitudinal diameters of the pelvic ring measured immediately before THA. RESULTS: There was a strong/moderate correlation in the values of PTPS between the Doiguchi and DRR methods. However, the value of PTPS calculated by the Doiguchi method was significantly lower than that calculated by DRR, and there was a partially direct match. On the other hand, there was no significant difference in the value of PT change from supine to lateral position between the Doiguchi and DRR methods. The PT changes based on both methods were strongly correlated, and the PT change calculated by the Doiguchi method was almost identical to that calculated by the DRR method. CONCLUSIONS: Doiguchi's pelvic tilt measurement method was validated for the first time. These results demonstrated that the ratio of the transverse and longitudinal diameters of the pelvic ring was an important factor defining the change in pelvic tilt. The slope in the linear function of the Doiguchi method was found to be almost the correct value, although the intercept of the linear function exhibited individual differences.

Delayed cortical bone healing due to impaired nuclear Nrf2 translocation in COPD mice.

The effect of the pathogenesis of chronic obstructive pulmonary disease (COPD) on bone fracture healing is unknown. Oxidative stress has been implicated in the systemic complications of COPD, and decreased activity of Nrf2 signaling, a central component of the in vivo antioxidant mechanism, has been reported. We investigated the process of cortical bone repair in a mouse model of elastase-induced emphysema by creating a drill hole and focusing on Nrf2 and found that the amount of new bone in the drill hole was reduced and bone formation capacity was decreased in the model mice. Furthermore, nuclear Nrf2 expression in osteoblasts was reduced in model mice. Sulforaphane, an Nrf2 activator, improved delayed cortical bone healing in model mice. This study indicates that bone healing is delayed in COPD mice and that impaired nuclear translocation of Nrf2 is involved in delayed cortical bone healing, suggesting that Nrf2 may be a novel target for bone fracture treatment in COPD patients.

Decrease in osteoporotic fracture in the western Kitakyushu region by the STOP-Fx study.

INTRODUCTION: The Seamless Treatment of Osteoporosis against Fractures (STOP-Fx) study was initiated to provide and continue therapeutic interventions for registered patients with osteoporotic fractures. MATERIALS AND METHODS: Women who visited six hospitals in the western Kitakyushu area for osteoporotic fractures between October 2016 and December 2018 were included in the study. Data collection for primary and secondary outcomes was conducted from October 2018 to December 2020, 2 years after STOP-Fx study enrollment. The primary outcome included the number of surgeries for osteoporotic fractures after the STOP-Fx study intervention, while secondary outcomes were the intervention rate of osteoporosis treatment, incidence and timing of secondary fractures, and factors associated with secondary fractures and loss to follow-up. RESULTS: Concerning the primary outcome, the number of surgeries for osteoporotic fractures decreased since the STOP-Fx study initiation: 813 in 2017, 786 in 2018, 754 in 2019, 716 in 2020, and 683 in 2021. Regarding the secondary outcome, of the 805 patients enrolled, 445 were available for follow-up at 24 months. Of the 279 patients who were untreated for osteoporosis at enrollment, 255 (91%) were on treatment at 24 months. There were 28 secondary fractures, which were associated with increased tartrate-resistant acid phosphatase-5b and decreased lumbar spine bone mineral density during enrollment in the STOP-Fx study. CONCLUSION: As the demographics and medical area served by six hospitals in the western Kitakyushu region have not changed significantly since the STOP-Fx study initiation, the STOP-Fx study may have contributed in decreasing the number of osteoporotic fractures.

Incidence and trend of antiresorptive agent-related osteonecrosis of the jaw from 2016 to 2020 in Kure, Japan.

We investigated the incidence/trend of osteonecrosis of the jaw by antiresorptive agent dose over a 5-year period in Kure city, Japan. The incidence was 24 times higher among osteoporosis patients with low-dose agents and 421 times higher among cancer patients with high-dose agents than in the population without agents. PURPOSE: We launched the registry system of osteonecrosis of the jaw (ONJ) cases in 2015 to investigate the trend in ONJ incidence. The purpose of our study was to estimate the ONJ incidence among patients with antiresorptive agent use by dosage and people without antiresorptive agent use in Kure and its trend from 2016 to 2020. METHODS: From 2016 to 2021, 98 eligible ONJ patients were enrolled. Medication-related ONJ (MRONJ) was diagnosed based on the American Association of Oral and Maxillofacial Surgeons criteria. The annual number of those with and without antiresorptive agents was obtained from the claims database. Antiresorptive agents used for cancer and osteoporosis patients were defined as high- and low-dose medications, respectively. RESULTS: The annual incidence of high-dose MRONJ was 2305.8 per 100,000 and that of low-dose MRONJ was 132.5 per 100,000, while the ONJ incidence among people without antiresorptive agents was 5.1 per 100,000. The incidence ratio was 23.6 (p < 0.001, 95% confidence interval (CI) 13.3-41.8) among osteoporosis patients who used low-dose antiresorptive agents and 420.6 (p < 0.001, 95% CI 220.8-801.4) among cancer patients who used high-dose agents compared with people who did not use these agents. MRONJ incidence increased from 2016 to 2020, but the incidence of high-dose MRONJ decreased, although this was nonsignificant. CONCLUSION: We demonstrated the incidence and trend of ONJ by antiresorptive agent dose over a 5-year period in Kure after launching the multiprofession study. This collaborative study for the early detection and prevention of ONJ will continue.

Validation of foot plantar pressure sensor data used to estimate standing, sitting, and moving durations in one working day.

BACKGROUND: Maintaining immovable postures for long durations might be a cause of low back pain. However, the relation between low back pain and the maintenance of postures for long durations has been unclear. Therefore, the durations of several postures in one working day should be measured to evaluate the risk of low back pain, although the available measuring methods are limited. To the best of our knowledge, no study has reported the development and investigation of a foot plantar pressure sensor for measurement of standing, sitting, and moving durations in daily work routines. Thus, in this study, we aimed to develop a foot plantar pressure sensor that could withstand long-term loads in the workplace. Furthermore, we aimed to evaluate the estimated results of standing, sitting, and moving durations among factory workers using the developed foot plantar pressure sensor. METHODS: The developed foot plantar pressure sensor obtained a percentage difference within ±5% to estimate standing, sitting, and moving durations in the laboratory. We measured foot plantar pressures of 20 factory workers to estimate standing, sitting, and moving activity in one working day using data obtained by the foot plantar pressure sensor. The estimated standing, sitting, and moving durations were compared with the human estimation of photo data obtained by a wearable camera. RESULTS: The agreement rate (Cohen's kappa coefficient) was 0.75 between the evaluation using the foot plantar pressure sensor data and human estimation using a wearable camera. Cohen's kappa coefficient was 0.81 in subjects who sat for ≥30% during daily work and 0.68 in subjects who sat for <30%. CONCLUSION: Our foot plantar pressure sensor effectively measured the standing, sitting, and moving durations in daily work that requires various movements and assumption of postures.

Trabecular Bone Volume Is Reduced, With Deteriorated Microstructure, With Aging in a Rat Model of Duchenne Muscular Dystrophy.

We aimed to clarify the effect of aging on trabecular bone volume and trabecular bone microstructure in a rat model of Duchenne muscular dystrophy (DMD). Six rats each of wild type (WT) and DMD model at 15 weeks of age, and 4 rats each at 30 weeks of age, were analyzed by dual energy X-ray absorptiometry and by micro-CT for analysis of trabecular and cortical bone of the femur. Bone mineral density was significantly lower in the DMD group than in the WT group at both 15 and 30 weeks of age. Micro-CT showed that trabecular bone volume and number were not significantly different between the two groups at 15 weeks, but at 30 weeks both were significantly lower in the DMD group than in the WT group. Connectivity density and structure model index were not significantly different between the two groups at 15 weeks, but at 30 weeks they differed significantly. No significant differences between the WT and DMD groups in cortical thickness and cortical area were evident at both 15 and 30 weeks. In conclusion, trabecular bone volume is significantly reduced, with deteriorated microstructure, with aging in a rat model of DMD.

Long Bones Exhibit Adaptive Responses to Chronic Low-Dose-Rate Ionizing Radiation despite its Lifespan-Shortening and Carcinogenic Effects on C57BL/6 Mice.

Ionizing radiation (IR) is a well-known carcinogen. High-dose-rate (HDR) IR is known to damage long bones (in terms of mass and structure), but the relationships among dose rates (particularly low-dose-rate [LDR] IR), long-bone condition, cancer incidence, and lifespan shortening remain elusive. The aim of this study was to elucidate the effects of LDR-IR on long-bone condition by comparing the long-term consequences of HDR- and LDR-IR exposure in mice. We utilized micro-computed tomography (µCT) scans of the long bones at similar ages (mean 77-96 weeks) to compare mice receiving approximately equivalent total doses of internal LDR-IR or external HDR-IR starting at 4 weeks of age, and their respective control groups. The lifespan-shortening effects of LDR-IR and HDR-IR were similar in these mixed-sex cohorts. Notably, compared to HDR-IR mice, mice internally exposed to chronic LDR-IR with continuous hypohematopoiesis showed a significantly higher trabecular bone connective density [femur: 247% (p = 0.0042), tibia: 169% (p = 0.0005)] and midshaft cortical bone thickness/area (femur: 130% [p = 0.0079]/120% [p = 0.021], tibia: 148% [p = 0.0004]/129% [p = 0.002]). Consistent with this result, when comparing 26-32 weeks post-IR with 2-8 weeks post-IR, compared to HDR-IR-treated mice, LDR-IR-treated mice exhibited higher levels of an osteoblast marker (OPG; p = 0.67 for HDR-IR, p = 0.068 for LDR-IR) and lower levels of an osteoclast marker (CTX-I; p = 0.0079 for HDR-IR, p = 0.72 for LDR-IR) despite significantly higher levels of inflammatory markers (CCL2 and CXCL1; p = 0.36-0.8 for HDR-IR, p = 0.013-0.041 for LDR-IR). These results suggest that long bones under chronic LDR-IR stress may exhibit an adaptive response to stresses such as chronic inflammation associated with IR-induced lifespan shortening. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Oxidative stress causes muscle structural alterations via p38 MAPK signaling in COPD mouse model.

INTRODUCTION: Sarcopenia is a complication of Chronic Obstructive Pulmonary Disease (COPD) that negatively affects physical activity and quality of life. However, the underlying mechanism by which COPD affects skeletal muscles remains to be elucidated. Therefore, we investigated the association between oxidative stress and structural alterations in muscles in elastase-induced emphysema mouse models. MATERIALS AND METHODS: Twelve-week-old male C57BL/6J mice were treated with either intratracheal porcine pancreatic elastase (PPE) dissolved in saline, or saline alone. The mice were euthanized 12 weeks after treatment, and the lungs and limb muscles were used for protein analysis of oxidative stress, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and muscle atrophy signaling pathway related with oxidative stress. Furthermore, C57BL/6J mice treated with PPE or saline were analyzed for the effects of oral administration of astaxanthin or p38 inhibitor. RESULTS: The weight of the soleus muscle, proportion of type I muscle fibers, and cross-sectional areas of muscle fibers in the PPE group were lower than those in the control group. Oxidative stress marker levels in the PPE group were elevated in skeletal muscles. The p38 MAPK signaling pathway was activated in the soleus muscles, leading to the activation of the ubiquitin-proteasome system and autophagy. Astaxanthin and p38 inhibitors attenuated alterations in muscle structure through the deactivation of the p38 MAPK signaling pathway. CONCLUSIONS: This study provides first evidence in COPD mouse model that oxidative stress trigger a series of muscle structural changes. Our findings suggest a novel target for sarcopenia in COPD.

Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice.

The hippocampus plays an important role in maintaining normal cognitive function and is closely associated with the neuropathogenesis of dementia. Wnt signaling is relevant to neuronal development and maturation, synaptic formation, and plasticity. The role of Wnt10a in hippocampus-associated cognition, however, is largely unclear. Here, we examined the morphological and functional alterations in the hippocampus of Wnt10a-knockout (Wnt10a-/-) mice. Neurobehavioral tests revealed that Wnt10a-/- mice exhibited spatial memory impairment and anxiety-like behavior. Immunostaining and Western blot findings showed that the protein expressions of ß-catenin, brain-derived neurotrophic factor, and doublecortin were significantly decreased and that the number of activated microglia increased, accompanied by amyloid-ß accumulation, synaptic dysfunction, and microglia-associated neuroinflammation in the hippocampi of Wnt10a-/- mice. Our findings revealed that the deletion of Wnt10a decreased neurogenesis, impaired synaptic function, and induced hippocampal neuroinflammation, eventually leading to hippocampal neurodegeneration and memory deficit, possibly through the ß-catenin signaling pathway, providing a novel insight into preventive approaches for hippocampus-dependent cognitive impairment.

Upregulation of the hypothalamo-neurohypophysial system and activation of vasopressin neurones attenuates hyperalgesia in a neuropathic pain model rat.

Arginine vasopressin (AVP) is a hypothalamic neurosecretory hormone well known as an antidiuretic, and recently reported to be involved in pain modulation. The expression kinetics of AVP and its potential involvement in the descending pain modulation system (DPMS) in neuropathic pain (NP) remains unclear. We investigated AVP expression and its effects on mechanical and thermal nociceptive thresholds using a unilateral spinal nerve ligation (SNL) model. All rats with SNL developed NP. Intensities of enhanced green fluorescent protein (eGFP) in the supraoptic and paraventricular nuclei, median eminence, and posterior pituitary were significantly increased at 7 and 14 days post-SNL in AVP-eGFP rats. In situ hybridisation histochemistry revealed significantly increased AVP mRNA expression at 14 days post-SNL compared with the sham control group. The chemogenetic activation of AVP neurones significantly attenuated mechanical and thermal hyperalgesia with elevated plasma AVP concentration. These analgesic effects were suppressed by pre-administration with V1a receptor antagonist. AVP neurones increased the neuronal activity of serotonergic dorsal raphe, noradrenergic locus coeruleus, and inhibitory interneurones in the spinal dorsal horn. These results suggest that the hypothalamo-neurohypophysial system of AVP is upregulated in NP and activated endogenous AVP exerts analgesic effects via the V1a receptors. AVP neurones may activate the DPMS.

Deficiency of Wnt10a causes female infertility via the ß-catenin/Cyp19a1 pathway in mice.

Wnt signaling is relevant for a wide range of biological processes, including reproductive function. The function of Wnt10a in female fertility, however, remains obscure. In the present study, we explored the structure and function of the female reproductive organs in Wnt10a knockout (KO) mice. The expression of ß-catenin signaling was significantly lower in the ovaries of the Wnt10a KO mice compared with wild-type (WT) mice. In addition, the estrous cycles were disrupted, ovarian follicles were diminished, and endometria were thinner, accompanied by lower serum estrogen levels, and higher testosterone and progesterone levels in Wnt10a KO mice. The expression of the ovarian cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) was significantly lower in Wnt10a KO mice. We detected no significant changes in the levels of the gonadotropins between WT and KO mice. Together, our findings indicate that deficiency of Wnt10a causes female infertility through ß-catenin and Cyp19a1signaling pathways in mice.

Isolation and Characterization of Synovial Mesenchymal Stem Cells Derived From Patients With Chronic Lateral Ankle Instability: A Comparative Analysis of Synovial Fluid, Adipose Synovium, and Fibrous Synovium of the Ankle Joint.

Background: Synovial mesenchymal stem cells (MSCs) have high proliferative potential and are considered an excellent source for stem cell therapy. Purposes: To isolate MSCs from the synovium of ankle joints in patients with chronic lateral ankle instability (CLAI) and to compare the characteristics of MSCs derived from the synovium anterior to the talus with those from the surrounding anterior talofibular ligament (ATFL) synovium. Study Design: Controlled laboratory study. Methods: The synovium was harvested from 2 locations in the ankle, the synovium anterior to the talus and the surrounding ATFL synovium, of 14 patients who underwent arthroscopic ATFL repair for CLAI without osteochondral lesions of the talus (OLTs). Synovial fluid was also harvested. MSCs were isolated from both types of synovial tissue, as well as synovial fluid. The number of MSCs in the synovium and their viability, proliferation, colony-forming units, and potential to differentiate into adipose, bone, and cartilage tissues were determined and compared between groups. Additionally, real-time polymerase chain reaction was used to assess the differentiation capacity of adipose, bone, and cartilage tissues from both samples. The Wilcoxon signed rank test was used to compare the sample weight, number of colonies, number of nucleated cells per colony, yield obtained, and phenotypic characteristics of MSCs derived from different locations of the synovium. Results: No significant differences were observed in the sample weight (P = .051), number of nucleated cells per milligram (P = .272), number of colonies (P = .722), and yield obtained (P = .099) between the 2 groups. MSCs could not be isolated from synovial fluid. The frequency of oil red O-positive adipogenic colonies (P = .028) and the expression of the adipsin gene (P < .05) were significantly increased in the cells from the synovium anterior to the talus compared to those in the cells from the surrounding ATFL synovium. However, chondrogenic and osteogenic potentials were not significantly different between the 2 groups. Conclusion: Synovial MSCs obtained from the ankle joint had self-renewal and multilineage differentiation potential, although the adipogenesis potential of MSCs from the synovium anterior to the talus was superior to that from the surrounding ATFL synovium. Clinical Relevance: Both the adipose synovium and fibrous synovium in the ankle joints of patients with CLAI may be a good source of MSCs for stem cell therapy applications, whereas synovial fluid appeared unsuitable.

Accurate cup placement using a portable navigation system during total hip arthroplasty based on pelvic orientation in the lateral decubitus position.

BACKGROUND: We previously proposed an accurate cup placement procedure using a portable navigation system (PNS) for total hip arthroplasty (THA) in the lateral decubitus position; however, the accuracy of our proposed procedure has not been shown, the aim of this study was to demonstrate the accuracy. METHODS: We prospectively analyzed 79 hips treated with primary THA; 40 hips treated until June 2020 were included in the conventional procedure (CP) group, and 39 hips treated from July 2020 were included in the modified procedure (MP) group. In the MP, pelvic orientation is considered to be the set coordinate axes in addition to the CP using the PNS. The accuracy was based on the difference between the navigation record (NR) and postoperative computed tomography measurement. RESULTS: The radiographic inclination (RI) and anteversion (RA) accuracies were 1.55° and 2.14°, respectively, in the MP group and 3.03° and 6.20°, respectively, in the CP group (p < 0.001). The error was within 5° of the NR for both the RI and RA in 34 in the MP group (87.2%) and 14 in the CP group (35.0%) (p < 0.001). The error was within 5° of the target angle (RI 40°, RA 15°) for both the RI and RA in 29 hips in the MP group (74.7%) and 12 in the CP group (30.0%) (p < 0.001). CONCLUSIONS: Our procedure with the consideration of pelvic orientation achieved dramatically improved the accuracy of PNS and was suitable to facilitate accurate cup placement.

Cleft Sign and Bone Marrow Edema of the Pubic Symphysis Are Associated With Sports and Bony Morphology in Patients With Femoroacetabular Impingement and Labral Tears.

BACKGROUND: The cleft sign (CS) and bone marrow edema (BME) are considered magnetic resonance imaging (MRI) findings signifying a pubic pathology, which is associated with groin pain; however, their relationship with bony morphology related to femoroacetabular impingement (FAI) has not been established. PURPOSE: To investigate the prevalence of CS and BME in symptomatic patients with acetabular labral tears and assess their possible association with bone morphology and sport-specific activities. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This study enrolled 418 patients (469 hips) undergoing hip arthroscopic surgery for labral tears. Also included were patients with labral tears in the setting of either hip dysplasia or borderline hip dysplasia who were undergoing endoscopic shelf acetabuloplasty combined with hip arthroscopic labral repair, cam osteoplasty, and capsular plication. All patients were screened for superior CS (SCS), inferior CS (ICS), and BME of the ipsilateral side of the pubis using 3-T MRI. We measured the following angles: lateral center edge (LCE), Sharp, Tönnis, vertical-central-anterior, and alpha. Then, we evaluated the relationship between patient characteristics and abnormal findings on MRI scans (preoperatively vs 1 year postoperatively). RESULTS: An overall 397 hips were included: 200 in men and 197 in women (mean ± SD age, 35.3 ± 16.0 years). There were hips in 214 athletes (53.9%) and hips in 183 nonathletes (46.1%). MRI findings revealed SCS, ICS, and BME in 18 (4.5%), 13 (3.3%), and 34 hips (8.6%), respectively. Abnormal MRI findings at the pubis were seen more often in athletes than nonathletes (23.8% vs 3.3%), and contact sports athletes had the most frequent abnormalities. There was no SCS in patients with an LCE angle <22°. SCS was more frequently seen in those who had an alpha angle ≥71°. More than 60% of abnormal findings at the pubis diminished after arthroscopic surgery that included FAI correction and labral repair. CONCLUSION: In patients with labral tears, CS and BME were seen more frequently in athletes versus nonathletes, especially contact athletes with FAI-related bony abnormalities. More than 60% of abnormal MRI pubis findings resolved after arthroscopic treatment of FAI.