Mesenchymal Stem Cells Preconditioned with Hypoxia and Dexamethasone Promote Osteoblast Differentiation Under Stress Conditions.

Bone marrow-derived mesenchymal stem cells (MSCs), which are capable of differentiating into osteoblasts, are used in effective regenerative therapies. MSCs must be prompted to differentiate into osteoblasts for MSC transplantation to be effective. In this study, osteoblast differentiation markers involved in bone formation were evaluated to investigate the stress resistance of bone marrow-derived rat MSCs to dexamethasone and hypoxia and their ability to differentiate into osteoblasts. MSCs were allowed to differentiate into osteoblasts for 21 days in three different environments (dexamethasone treatment, hypoxic conditions [1% oxygen], or both). Osteoblast differentiation potential was evaluated according to alkaline phosphatase levels and a mineralisation assay. Immunofluorescence staining was used to determine the protein expression of the osteoblast differentiation markers type I collagen and osteopontin. MSCs differentiated into osteoblasts under hypoxic conditions but differentiated more slowly upon treatment with dexamethasone and dexamethasone plus hypoxia relative to the control. MSCs preconditioned with dexamethasone or hypoxia and then allowed to differentiate into osteoblasts under similar conditions differentiated comparably to control MSCs. MSCs that developed resistance to dexamethasone or hypoxia differentiated more quickly into osteoblasts than those that did not. The findings suggest that increasing the resistance of MSCs to stress by preconditioning them via dexamethasone or hypoxia exposure could result in more rapid differentiation into osteoblasts following transplantation.

A novel cell source for therapy of knee osteoarthritis using atelocollagen microsphere-adhered adipose-derived stem cells: Impact of synovial fluid exposure on cell activity.

Introduction: Administration of adipose-derived stem cells (ADSCs) into the joint cavity has been shown to alleviate the symptoms of knee osteoarthritis (OA) by releasing exosomes and anti-inflammatory cytokines. However, the therapeutic effect of these cells is limited by their rapid disappearance after administration. Thus, it is necessary to prolong cell survival in the joint cavity. This study aimed to investigate the potential application of ADSCs adhered to atelocollagen microspheres (AMSs) for cell therapy of knee OA. Methods: ADSCs were cultured for 2, 4, and 7 days in AMS suspension or adherent culture dishes. The supernatants were analyzed for IL-10 and exosome secretion via enzyme-linked immunosorbent assay and Nanosight. The effect of AMS was compared with that of adherent-cultured ADSCs (2D-cultured ADSCs) using transcriptome analysis. Moreover, the solubility of AMS and viability of ADSCs were evaluated using synovial fluid (SF) from patients with knee OA. Results: Compared with 2D-cultured ADSCs, AMS-cultured ADSCs exhibited a significant increase in secretion of exosomes and IL-10, and the expression of several genes involved in extracellular matrix and immune regulation were altered. Furthermore, when AMS-cultured ADSCs were cultured in SF from knee OA patients to mimic the intra-articular environment, the SF dissolved the AMSs and released viable ADSCs. In addition, AMS-cultured ADSCs showed significantly higher long-term cell viability than 2D-cultured ADSCs. Conclusion: Increased survival of AMS-adhered ADSCs was observed in the intra-articular environment, and AMSs were found to gradually dissipate. These results suggest that AMS-adhered ADSCs are promising source for cell therapy of knee OA.

Radiographic Evaluation and Changes in Bone Density of the Humeral Side after Reverse Total Shoulder Arthroplasty.

After artificial joint surgery, bone density may decrease around the artificial joint; thus, postoperative bone density evaluation around the artificial joint is crucial. We investigated changes in bone mineral density and performed radiographic evaluation around the stem after reverse shoulder arthroplasty (RSA) surgery in 17 males (18 shoulders) and 19 females (19 shoulders), aged >65 years, with >1-year follow-up. In total, 20 and 17 cases involved massive rotator cuff tears and rotator cuff tear arthropathy, respectively. The Comprehensive Reverse Shoulder System (Standard Ingrowth) was used for all cases and cement was used in eight patients due to bone fragility. We examined lucent lines, loosening, bone resorption, and spot welds in non-cemented cases using plain radiography and postoperative bone density changes around the stem using dual-energy X-ray absorptiometry (DEXA). Lucent lines and bone resorption occurred in 5 (13.5%) and 19 (51.4%) shoulders, respectively. No loosening occurred. Compared to stem bone density at 2 weeks postoperatively, the decrease rate was the largest in the proximal medial humerus. One-year postoperative bone density was not related to sex, age, cement use, or preoperative diagnosis. Higher preoperative bone density was better maintained postoperatively. Furthermore, 1 year post RSA, spot welds were observed in approximately 48.2% of cases at the distal medial portion of the stem coating, and bone resorption occurred in the proximal medial humerus in 43.2% of cases. Therefore, postoperative bone density is related to preoperative bone density, suggesting the importance of maintaining high preoperative bone density.

Septic Arthritis of Cervical Spine Facet Joints: A Case Report and Review of Imaging.

BACKGROUND Septic arthritis of the facet joint (SAFJ) has been considered a rare type of spinal infection. However, because of the aging of the population, the increase in compromised hosts, and the increase in MRI use in recent years, the number of reports has been increasing. We report the clinical progress of a rare case of septic arthritis of the cervical facet joint (SACFJ) with some imaging considerations, and we compare our findings with existing reports of SACFJ. CASE REPORT A 73-year-old Japanese woman presented with fever, paralytic symptoms, and paresthesia of the upper limbs. Here, we report a case of SACFJ in which MRI findings allowed early diagnosis, and a favorable course was obtained by conservative treatment with antibiotics. Although MRI performed 93 days after the initiation of treatment showed a slight residual signal change in the facet joints, no symptoms had recurred by the sixth month after hospital discharge. CONCLUSIONS If a patient develops neurological symptoms such as paralysis with fever and increased inflammatory response, the physician must consider the possibility of pyogenic spondylitis, including SACFJ, and order an MRI. Epidural abscess is almost inevitable in SACFJ, and surgical treatment, including abscess drainage, is required if spinal cord or paralytic symptoms progress. For patients with SACFJ, as well as pyogenic spondylitis, MRI may not be useful in determining treatment efficacy.

A Case of Axillary Web Syndrome Caused by Venous Blood Sampling.

Axillary web syndrome (AWS) occurs after breast cancer surgery, sentinel lymph node dissection, or sentinel lymph node biopsy. Here, cord-like structures from the axilla to the forearm limit the range of motion of the shoulder joint and cause pain. Although the etiology is unknown, AWS has been attributed to the blockage of normal lymphatic flow. Here, we report a novel case of AWS after venous blood sampling in a patient. A healthy, 31-year-old male patient experienced pain with a limited range of motion of the shoulder joint the day after venous blood was collected from the left upper extremity for a medical checkup, and he presented to an orthopedic outpatient clinic on the day. Palpation of the axillary region disclosed a cord-like structure in the axillary region of the shoulder joint during abduction, and the patient was diagnosed with AWS. The cord-like structure was noted to be a hypoechogenic luminal structure on ultrasound (US) examination of the axilla, extending from the axilla to below the ulnar cutaneous vein from which the blood was drawn. In patients with pain and a limited range of motion of the shoulder joint, only the shoulder joint is examined during an orthopedic examination. It is important to obtain appropriate physical findings for possible AWS.

Efficacy of Rectal Systemic Administration of Mesenchymal Stem Cells to Injury Sites via the CXCL12/CXCR4 Axis to Promote Regeneration in a Rabbit Skeletal Muscle Injury Model.

Mesenchymal stem cells (MSCs) have been transplanted directly into lesions or injected intravenously. The administration of MSCs using these delivery methods requires specialized knowledge, techniques, and facilities. Here, we describe intrarectal systemic administration of MSCs, a simple, non-invasive route for homing to the injury sites to promote the regeneration of skeletal muscle injuries. Using a cardiotoxin (CTX)-induced rabbit skeletal muscle injury model, homing to the site of muscle injury was confirmed by intrarectal administration of MSCs; the time required for homing after intrarectal administration was approximately 5 days. In addition, the C-X-C chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor-4 (CXCR4) axis was found to be involved in the homing process. Histopathological examinations showed that skeletal muscle regeneration was promoted in the MSCs-administered group compared to the CTX-only group. Myosin heavy polypeptide 3 (Myh3) expression, an indicator of early muscle regeneration, was detected earlier in the intrarectal MSCs group compared to the CTX-only group. These findings indicate that intrarectal administration of MSCs is effective in homing to the injured area, where they promote injury repair. Since intrarectal administration is a simple and non-invasive delivery route, these findings may be valuable in future research on stem cell therapy.

Collarless Polished Tapered Stems of Identical Shape Provide Differing Outcomes for Stainless Steel and Cobalt Chrome: A Biomechanical Study.

Cemented polished tapered femoral stems (PTS) made of cobalt-chrome alloy (CoCr) are a known risk factor for periprosthetic fracture (PPF). The mechanical differences between CoCr-PTS and stainless-steel (SUS) PTS were investigated. CoCr stems having the same shape and surface roughness as the SUS Exeter® stem were manufactured and dynamic loading tests were performed on three each. Stem subsidence and the compressive force at the bone-cement interface were recorded. Tantalum balls were injected into the cement, and their movement was tracked to indicate cement movement. Stem motions in the cement were greater for the CoCr stems than for the SUS stems. In addition, although we found a significant positive correlation between stem subsidence and compressive force in all stems, CoCr stems generated a compressive force over three times higher than SUS stems at the bone-cement interface with the same stem subsidence (p < 0.01). The final stem subsidence amount and final force were greater in the CoCr group (p < 0.01), and the ratio of tantalum ball vertical distance to stem subsidence was significantly smaller for CoCr than for SUS (p < 0.01). CoCr stems appear to move more easily in cement than SUS stems, which might contribute to the increased occurrence of PPF with the use of CoCr-PTS.

The Possibility of IPC to Prevent Ischemic-Reperfusion Injury in Skeletal Muscle in a Rat.

Blood removal with air tourniquets for a long time induces muscle damage after reperfusion. Ischemic preconditioning (IPC) has a protective effect against ischemia-reperfusion injury in striated muscle and myocardium. However, the mechanism of action of IPC on skeletal muscle injury is unclear. Thus, this study aimed to investigate the effect of IPC in reducing skeletal muscle damage caused by ischemia-reperfusion injury. The hindlimbs of 6-month-old rats were wounded with air tourniquets at a carminative blood pressure of 300 mmHg on the thighs. Rats were divided into the IPC (-) group and the IPC (+) group. The vascular endothelial growth factor (VEGF), 8-hydroxyguanosine (8-OHdG), and cyclooxygenase 2 (COX-2) were investigated by protein levels. Quantitative analysis of apoptosis was performed using the TUNEL method. Compared with the IPC (-) group, the IPC (+) group retained the VEGF expression, and the COX-2 and 8-OHdG expressions were suppressed. The proportion of apoptosis cells decreased in the IPC (+) group compared with the IPC (-) group. IPC in skeletal muscles proliferated VEGF and suppressed inflammatory response and oxidative DNA damage. IPC has the potential to reduce muscle damage after ischemia-reperfusion.

Synovial Fluid Derived from Human Knee Osteoarthritis Increases the Viability of Human Adipose-Derived Stem Cells through Upregulation of FOSL1.

Knee osteoarthritis (Knee OA) is an irreversible condition that causes bone deformity and degeneration of the articular cartilage that comprises the joints, resulting in chronic pain and movement disorders. The administration of cultured adipose-derived stem cells (ADSCs) into the knee joint cavity improves the clinical symptoms of Knee OA; however, the effect of synovial fluid (SF) filling the joint cavity on the injected ADSCs remains unclear. In this study, we investigated the effect of adding SF from Knee OA patients to cultured ADSCs prepared for therapeutic use in an environment that mimics the joint cavity. An increase in the viability of ADSCs was observed following the addition of SF. Gene expression profiling of SF-treated ADSCs using DNA microarrays revealed changes in several genes involved in cell survival. Of these genes, we focused on FOSL1, which is involved in the therapeutic effect of ADSCs and the survival and proliferation of cancer stem cells. We confirmed the upregulation of FOSL1 mRNA and protein expression using RT-PCR and western blot analysis, respectively. Next, we knocked down FOSL1 in ADSCs using siRNA and observed a decrease in cell viability, indicating the involvement of FOSL1 in the survival of ADSCs. Interestingly, in the knockdown cells, ADSC viability was also decreased by SF exposure. These results suggest that SF enhances cell viability by upregulating FOSL1 expression in ADSCs. For therapy using cultured ADSCs, the therapeutic effect of ADSCs may be further enhanced if an environment more conducive to the upregulation of FOSL1 expression in ADSCs can be established.

Angular changes in pelvic tilt and cup orientation at a minimum of eighteen years after primary total hip arthroplasty with an uncemented cup.

BACKGROUND: Changes in pelvic tilt angle (PTA) and cup orientation have been reported in patients after total hip arthroplasty, but the current literature generally has a brief follow-up period. This study will be the first to report PTA and cup orientation changes in the supine position for a minimum 18 years after total hip arthroplasty (THA) and investigate the factors associated with pelvic tilt and cup orientation changes. METHODS: In this study, 101 patients (120 hips) who underwent THA were retrospectively analyzed. The aims of our study were to evaluate the PTA and cup orientation change over 18 years after THA to assess differential PTA, cup inclination, and anteversion. We also investigated whether factors such as gender, body mass index, and age have any influence on PTA and cup orientation after THA. RESULTS: Patients showed a significant incremental change in PTA pre-operatively, immediately post-operatively, and at final follow-up. Cup orientation increased significantly at the final follow-up compared to the immediate post-operative period. Gender subgroup analysis showed that PTA was significantly greater in females than in males at the final follow-up (p = 0.025). Age subgroup analysis showed that PTA was significantly greater in the over 60 years group than in the other groups. CONCLUSION: Our patients showed significant changes in PTA and cup orientation at a minimum 18 years after surgery, especially in females over 60 years. Female patients over 60 are a risk factor after THA.

Does the Dual Mobility Cup Reduce Dislocation After Primary Total Hip Arthroplasty in Elderly Patients at High Risk of Dislocation?

OBJECTIVE: The dual mobility cup (DMC) is designed to extend the longevity of the prosthesis by improving stability, enhancing the range of motion, and decreasing impingement without increasing wear. We hypothesized that DMC would reduce the risk of dislocation in elderly patients. This study aimed to investigate the clinical and radiographic outcomes of DMC-total hip arthroplasty (THA) in elderly patients at high risk of dislocation. METHODS: From June 2016 to March 2020, 94 patients with a mean age of 77.7 years (97 hips) who underwent a posterolateral approach for DMC-THA in our department were followed up for at least one year. Preoperative and postoperative pelvic tilt angles (PTA) and DMC orientation were prospectively collected for all patients. Intraoperative and postoperative complications were recorded. A parametric test was used for normal distribution, and a non-parametric test was used for non-normal distribution. RESULTS: Abduction and anteversion angles of the cup were 42.4 and 18.0° in the supine position immediately postoperative. The average PTA for patients in the supine and standing positions were 26.5 and 34.5°, respectively. When moving from the supine to the standing position, patients experienced a mean posterior pelvic tilt of 9°. No intraoperative acetabular-related complications were recorded. Postoperative complications included early infection in one patient (1.0%) and dislocation in one patient (1.0%). CONCLUSION: Our study demonstrates that DMC-THA provides satisfactory short-term outcomes in elderly patients at a high risk of dislocation, regardless of the change in PTA resulting from postural transition.

Inhibitory effect of taurine on rotator cuff degeneration via mitochondrial protection.

OBJECTIVES: Degenerative rotator cuff tears do not heal spontaneously, necessitating surgical intervention. This makes prevention crucial, but effective prophylactic measures are currently lacking. Oxidative stress has recently been implicated as a cause of degenerative rotator cuff tears, while mitochondrial injury has been reported in the development of age-related rotator cuff degeneration. Taurine, which has antioxidant properties, has been found to be effective in the treatment of various mitochondrial abnormalities. This prompted us to investigate the inhibitory effect of taurine and some other antioxidants against rotator cuff degeneration using tenocytes. METHODS: Hydrogen peroxide (H2O2, 2 mM) was added to tenocytes in medium with 0.8 µM taurine (Group TAU), medium with 100 µM α-tocopherol (Group E), and medium with 150 µM ascorbic acid (Group C), then each medium was cultured for 24 h. Tenocytes supplemented with 2 mM H2O2 alone were similarly cultured for 24 h (Group H2O2). In each group, immunostaining was performed for the oxidative stress marker 8-hydroxy-2'-deoxyguanosine and advanced glycation end products (AGE), which contribute to the development of age-related rotator cuff degeneration. In addition, levels of reactive oxygen species were measured using a cell-based assay kit, and results were compared. Immunostaining was also performed for indices of apoptosis (caspase-9, cleaved caspase-3 and Bcl-2), and Western blotting was used to quantify activation of caspase-9 at an early stage in each group. RESULTS: Oxidative stress and AGE levels were decreased in the E and C groups. Levels of all parameters were reduced in the TAU group. CONCLUSIONS: Taurine showed preventative effects against rotator cuff degeneration. The simple method of administration and paucity of side effects make clinical application easy, and the clear potential as a novel prophylactic strategy against degenerative rotator cuff tear warrants further study.

A morphological study of adipose-derived stem cell sheets created with temperature-responsive culture dishes using scanning electron microscopy.

Adipose-derived stem cell (ADSC) sheets have potential to be effective in various therapies. In this study, we first demonstrated that a cell sheet composed of human ADSCs could be created using a new temperature-responsive culture dish from the DIC Corporation. The dish can cause detachment of adherent cells due to temperature changes, but a few morphological analyses have evaluated the presence or absence of damage on the detached surface of cell sheet. To characterize our ADSC sheet, we tried to observe the surface of ADSC sheets with scanning electron microscope (SEM) using the ionic liquid, which enables the rapid preparation of samples. No damage was found on the surface of the ADSC sheets on the side that had been in contact with the surface of the culture dishes. In addition, when the transcriptomes of the harvested cell sheets were compared with those of monolayer cultures, no up-regulation of cell death related genes were detected. These results propose that the detachment from temperature-responsive culture dish causes no serious damage on the prepared ADSC sheet. It is also suggested that the SEM with ionic liquids is a useful and rapid method for the analysis of ADSC sheets for therapy.

Evaluation of the Usefulness of Human Adipose-Derived Stem Cell Spheroids Formed Using SphereRing® and the Lethal Damage Sensitivity to Synovial Fluid In Vitro.

Osteoarthritis (OA) is an irreversible degenerative condition causing bone deformation in the joints and articular cartilage degeneration with chronic pain and impaired movement. Adipose-derived stem cell (ADSC) or crushed adipose tissue injection into the joint cavity reportedly improve knee function and symptoms, including pain. Stem cell spheroids may be promising treatment options due to their anti-inflammatory and enhanced tissue regeneration/repair effects. Herein, to form human ADSC spheroids, we used first SphereRing® (Fukoku Co., Ltd., Ageo, Japan), a newly developed rotating donut-shaped tube and determined their characteristics by DNA microarray of mRNA analysis. The variable gene expression cluster was then identified and validated by RT-PCR. Gene expression fluctuations were observed, such as COL15A1 and ANGPTL2, related to vascular endothelial cells and angiogenesis, and TNC, involved in tissue formation. In addition, multiplex cytokine analysis in the medium revealed significant cytokines and growth factors production increase of IL-6, IL-10, etc. However, ADSC administration into the joint cavity involves their contact with the synovial fluid (SF). Therefore, we examined how SF collected from OA patient joint cavities affect 2D-culture ADSCs and ADSC spheroids and observed SF induced cell death. ADSC spheroids could become promising OA treatment options, although studying the administration methods and consider their interaction with SF is essential.

A Novel Minimally Invasive Spherical Periacetabular Osteotomy: Pelvic Ring Preservation and Patient-Specific Osteotomy by Preoperative 3-Dimensional Templating.

BACKGROUND: Spherical periacetabular osteotomy (SPO) is a novel osteotomy involving splitting the teardrop, using patient-specific preoperative planning, and requiring only a 7-cm skin incision. We report preoperative planning methods and short-term results of SPO. METHODS: In preoperative planning, computed tomography (CT) images were imported into 3-dimensional templating software. The radius of the curved chisel was mapped to pass through the teardrop, the infracotyloid groove of the ischium, and the area between the anterior superior iliac spine and the anterior inferior iliac spine. The osteotomy height and the predicted depth of osteotome insertion were measured, and those values were reproduced during surgery. We performed a retrospective analysis of data on 52 consecutive patients (55 hips) with hip dysplasia who underwent SPO and were followed for at least 2 years: 27 hips had Tönnis grade 0, 21 had grade 1, and 7 had grade 2. The mean age at surgery was 38 years (range, 17 to 56 years). The rotated bone fragment and iliac crest were fixed with absorbable screws. Statistical analysis was performed with the paired t test. RESULTS: The mean (range) of the lateral center-edge and sourcil angles were 6.0° (-20° to 18°) and 26.0 (13° to 38°), respectively, before surgery and 30.0° (15° to 43°) and 3.8° (-4° to 27°), respectively, after surgery (p < 0.001). However, 11 hips (20%) showed a loss of correction of bone rotation (<3 mm) or the sourcil angle (<3°). Radiographs showed bone union in all hips within 3 months after the surgery. Early second surgery related to absorbable screws was performed in 2 hips. No patient had required conversion to total hip arthroplasty at the time of writing. Clinical scores were significantly improved at the 2-year follow-up (p < 0.001). Paresthesia of the lateral femoral cutaneous nerve area was very common but had resolved in 92% of the patients at the 2-year follow-up. CONCLUSIONS: SPO is a novel minimally invasive periacetabular osteotomy that has the potential disadvantage of early loss of correction (observed in 20% of the hips in the present study) but may provide the benefit of decreasing the risk of nonunion at the pubis osteotomy site. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Long-Term Outcomes for Cementless Anatomic Femoral Components, Compared by Area of Porous Coating, in Patients Younger Than 50 Years Treated for Hip Dysplasia.

BACKGROUND: We investigated whether the proximal circumferential porous coating of cementless stems would make implant survival of >20 years possible in young patients. METHODS: Data for patients younger than 50 years with hip dysplasia who had an anatomic stem implanted with a proximal porous coating with hydroxyapatite/tricalcium phosphate were reviewed. Noncircumferential porous (non-C-type) stems were used in 17 hips (13 cases), and circumferential porous (C-type) stems were used in 87 hips (68 cases). Acetabular components with conventional polyethylene were used for all hips. The mean ages at surgery for patients with non-C-type stems and those with C-type stems were 43.3 and 44.7 years, respectively. Stems that had not loosened were retained at the time of acetabular revision. The average duration of follow-up for patients with non-C-type stems was 26.9 years and was 22.3 years for those with C-type stems. RESULTS: Mean survival rates as determined by the Kaplan-Meier method were 74.9% at 20 years and 59.9% at 25 years for non-C-type stems and were 100% at 20 years and 94.0% at 25 years for C-type stems. The survivorship for C-type stems was significantly higher than that for non-C-type stems (P < .01). Focal osteolysis in the shoulder of 37 hips with C-type stems suppressed the spread of osteolysis to the distal femur. CONCLUSION: Anatomic femoral stems with a circumferential porous coating provide excellent durability in patients with hip dysplasia who are 50 years of age or younger. LEVEL OF EVIDENCE: Therapeutic Level IV.

Resistance of bone marrow mesenchymal stem cells in a stressed environment - Comparison with osteocyte cells.

Introduction: Recently, the efficacy of mesenchymal stem cells (MSCs) mediated by their tissue repair and anti-inflammatory actions in the prevention and therapy of various disorders has been reported. In this research, our attention was focused specifically on the prevention and therapy of glucocorticoid-induced osteonecrosis. We investigated the stress resistance of MSC against glucocorticoid administration and hypoxic stress, which are factors known to induce osteocytic cell death. Materials and Methods: Mouse bone cells (MLO-Y4) and bone-marrow derived mouse MSCs were exposed to dexamethasone (Dex), hypoxia of 1% oxygen or both in vitro. Mitochondrial membrane potentials were estimated by mitochondria labeling with a cell-permeant probe (Mito tracker red); expression of these apoptosis-inducing molecules, oxidative stress marker (8-hydroxy-2'-deoxyguanosine), caspase-3, -9, and two apoptosis-inhibiting molecules, energy-producing ATP synthase (ATP5A) and X-linked inhibitor of apoptosis protein (XIAP), were analyzed by both immunofluorescence and western blot. Results: With exposure to either dexamethasone or hypoxia, MLO-Y4 showed reduced mitochondrial membrane potential, ATP5A and upregulation of 8-OHdG, cleaved caspases and XIAP. Those changes were significantly enhanced by treatment with dexamethasone plus hypoxia. In MSCs, however, mitochondrial membrane potentials were preserved, while no significant changes in the pro-apoptosis or anti-apoptosis molecules analyzed were found even with exposure to both dexamethasone and hypoxia. No such effects induced by treatment with dexamethasone, hypoxia, or both were demonstrated in MSCs at all. Discussion: In osteocyte cells subjected to the double stresses of glucocorticoid administration and a hypoxic environment osteocytic cell death was mediated via mitochondria. In contrast, MSC subjected to the same stressors showed preservation of mitochondrial function and reduced oxidative stress. Accordingly, even under conditions sufficiently stressful to cause the osteocytic cell death in vivo, it was thought that the function of MSC could be preserved, suggesting that in the case of osteonecrosis preventative and therapeutic strategies incorporating their intraosseous implantation may be promising.

Catastrophic failure of cup revision hip arthroplasty due to undiagnosed Paget disease of bone: A case report.

INTRODUCTION: Paget's disease of bone (PDB) is a localized chronic osteopathy, apparently not genetic in origin, and frequently diagnosed from incidental radiographic images. The disease is characterized by deformation, hypervascularity, and structural weakness of the bone and by changes in joint biomechanics. Most cases of PDB can be easily diagnosed from radiographic findings, but monostotic cases may be problematic and require invasive procedures. PRESENTATION OF CASE: A 70-year-old woman had re-revision surgery for early catastrophic failure of an isolated cup revision hip arthroplasty because of undiagnosed PDB 21 years after the primary total hip arthroplasty. To identify the pathomechanism of early failure, we performed bone biopsy on the right iliac crest. Histopathological findings showed a mosaic pattern in the bone characteristic of PDB. Prior to the planned re-revision surgery, we treated the PDB with denosumab until the patient's serum level of alkaline phosphatase (ALP) was within the normal limits. Two months after denosumab treatment, we performed re-revision hip arthroplasty using a structural allograft and a Kerboull-type reinforcement device. DISCUSSION: The delay in correct diagnosis of PDB was associated with the rapid destruction of pelvic bone. The preoperative use of antipagetic medication could decrease the risk of implant loosening and may be warranted to mitigate that risk. CONCLUSION: In patients with a failed arthroplasty, thoughtful evaluation is warranted for preoperative antipagetic medication in order to reduce PDB activity and potentially decrease the risk of implant loosening. This paper offers some steps for such risk reduction in the workup before revision surgery.

Dual mobility acetabular construct with freedom constrained liner for treatment of recurrent dislocations after total hip arthroplasty: A case report and literature review.

INTRODUCTION: Recurrent dislocation after total hip arthroplasty (THA) using the dual mobility cup system can present challenges, while dual-mobility THA bearings can improve stability in both primary and revision total hip arthroplasties. PRESENTATION OF CASE: A 72-year-old woman with a history of schizophrenia underwent a left primary THA using the G7 dual mobility system. Two postoperative posterior dislocations occurred within 2 months post-surgery. The patient underwent revision surgery in which the metal liner and dual mobility head were exchanged using the Freedom constrained liner system without revision of the cup and stem. As of this writing, 28 months after the revision surgery, no further dislocations have occurred. The implants are stable, and the patient has good range of motion. DISCUSSION: Dual-mobility bearings are utilized to improve stability in both primary and revision total hip arthroplasties, but even if the dual mobility system is chosen, it sometimes fails to prevent postoperative dislocation. Although a relatively high failure rate has been reported in THA using the constrained liner system, this patient's clinical course suggests that the G7 Freedom constrained liner system can be an efficacious option for some patients with unstable hip joints who undergo THA using the dual mobility system. CONCLUSION: A modern constrained liner system such as the G7 Freedom liner may provide an improved salvage solution for joint instability in dual mobility THA.

Taurine Inhibits Glucocorticoid-Induced Bone Mitochondrial Injury, Preventing Osteonecrosis in Rabbits and Cultured Osteocytes.

Mitochondrial injury has recently been implicated in the pathogenesis of glucocorticoid-induced osteonecrosis. Using cultured osteocytes and a rabbit model, we investigated the possibility that taurine (TAU), which is known to play a role in the preservation of mitochondrial function, might also prevent the development of osteonecrosis. To reduplicate the intraosseous environment seen in glucocorticoid-induced osteonecrosis, dexamethasone (Dex) was added to MLO-Y4 cultured in 1% hypoxia (H-D stress environment). An in vitro study was conducted in which changes in mitochondrial transcription factor A (TFAM), a marker of mitochondrial function, and ATP5A produced by mitochondria, induced by the presence/absence of taurine addition were measured. To confirm the effect of taurine in vivo, 15 Japanese White rabbits were administered methylprednisolone (MP) 20 mg/kg as a single injection into the gluteus muscle (MP+/TAU- group), while for 5 consecutive days from the day of MP administration, taurine 100 mg/kg was administered to 15 animals (MP+/TAU+ group). As a control 15 untreated rabbits were also studied. The rabbits in each of the groups were sacrificed on the 14th day after glucocorticoid administration, and the bilateral femora were harvested. Histopathologically, the incidence of osteonecrosis was quantified immunohistochemically by quantifying TFAM and ATP5A expression. In the rabbits exposed to an H-D stress environment and in MP+/TAU- group, TFAM and ATP5A expression markedly decreased. With addition of taurine in the in vitro and in vivo studies, the expression of TFAM and ATP5A was somewhat decreased as compared with Dex-/hypoxia- or MP-/TAU- group, while improvement was noted as compared with Dex+/hypoxia+ or MP+/TAU- group. In rabbits, the incidence of osteonecrosis was 80% in MP+/TAU- group, in contrast to 20% in the taurine administered group (MP+/TAU+), representing a significant decrease. Since taurine was documented to exert a protective effect on mitochondrial function by inhibiting the mitochondrial dysfunction associated with glucocorticoid administration, we speculated that it might also indirectly help to prevent the development of osteonecrosis in this context. Since taurine is already being used clinically, we considered that its clinical application would also likely be smooth.