Number of osteoporosis patients is increasing continuously in Japan, which has a super-aged society. Pain is not considered a typical symptom of osteoporosis patients, if they have no fractures. ...However, low back pain is one of the most frequent complaints in elderly people, osteoporosis is common in elderly persons, and osteoporosis might cause such low back pain. In this review, I will discuss my presentation at the symposium of The 29th Annual Meeting of the Japanese Society for the Study of Low Back Pain.
Osteoclasts are multinuclear giant cells derived from osteoclast/macrophage/dendritic cell common progenitor cells. The most characteristic feature of osteoclasts is multinucleation resulting from ...cell-cell fusion of mononuclear osteoclasts. Osteoclast cell-cell fusion is considered essential for re-organization of the cytoskeleton, such as the actin-ring and ruffled boarder to seal the resorbing area and to secret protons, respectively, to resorb bone; the fusion process is thus critical for osteoclast function. Various molecules, such as E-cadherin and macrophage fusion receptor (MFR), have been identified as regulators of osteoclast or macrophage cell-cell fusion. Laboratory production of osteoclasts used to be performed in a co-culture of osteoclast progenitors with osteoblastic cells, but recent advances in the identification of nuclear factor of kappa B ligand (RANKL) enabled the isolation of osteoclast-specific molecules involving osteoclast cell-cell fusion and differentiation regulators from purified osteoclast mRNA, since osteoclasts can be formed without osteoblasts. The essential cell-cell fusion regulator, dendritic cell-specific transmembrane protein (DC-STAMP), was isolated by a cDNA subtractive screen between mononuclear macrophages and RANKL-induced multinuclear osteoclasts. The cell-cell fusion of osteoclasts and foreign body giant cells (FBGCs) was completely abrogated in DC-STAMP-deficient mice in vivo and in vitro. Bone resorbing activity was significantly reduced but was still detected in DC-STAMP-deficient osteoclasts. DC-STAMP expression is positively regulated by two transcriptional factors: nuclear factor of activated T cells 1 (NFATc1) and c-Fos, both of which are essential for osteoclast differentiation. Furthermore, a novel osteoclastogenesis-regulating pathway involving two transcriptional repressors B cell lymphoma 6 (Bcl6) and B lymphocyte-induced maturation protein 1 (Blimp1) under RANKL stimulation has been discovered. The expression of osteoclastic genes such as DC-STAMP, NFATc1, and Cathepsin K, as well as osteoclast differentiation, was inhibited by Bcl6. Bcl6-deficient mice showed enhanced osteoclastogenesis and reduced bone mass, whereas osteoclast-specific Blimp1-conditional knockout mice showed elevated Bcl6 expression, osteoclastic gene expression, and osteoclast differentiation and increased bone mass. In this review, recent advances in our understanding of the regulators of osteoclast differentiation and cell-cell fusion are discussed.
•Psoas major muscle index within 1 month was associated with independent walking.•Total bilirubin at start of physiotherapy was associated with independent walking.•Underlying disease was associated ...with achieving independent walking.•Measuring psoas major skeletal muscle mass evaluates independent walking.
Mobility affects the ability of patients to live independently post-discharge. This study aimed to identify factors affecting the achievement of independent walking in patients after living donor liver transplantation (LDLT).
This retrospective cohort study involved 40 patients who had undergone LDLT for severe hepatic dysfunction (Child-Pugh class C) in the Department of Transplant Surgery of our hospital between January 2010 and October 2019 and received physiotherapy during hospital admission. To identify factors associated with independent walking, we classified patients based on their ability to walk independently. We performed multiple logistic regression analyses with the patients' attributes, biochemical tests, and physical function, considering the achievement or non-achievement of independent walking as dependent variables, and factors that were significantly different between the 2 groups in the univariate analysis (P < .05) as independent variables, after adjusting for age, sex, and body mass index. Moreover, we calculated cutoff values from the receiver operating characteristic (ROC) curves.
All patients suffered from severe hepatic dysfunction (Child-Pugh class C). The mobility Functional Independence Measure score following rehabilitation was positively correlated with the psoas major muscle index within 1 month after LDLT and at the beginning of physiotherapy. The only factor associated with achieving independent walking at the end of physiotherapy (on discharge) was the psoas major muscle index within 1 month of LDLT (odds ratio = 35.03, P < .05), and its cutoff value, calculated from the ROC curves curve, was 4.46.
Psoas major skeletal muscle mass is a reliable index for independent walking after LDLT.
The aging of the population worldwide has sharply increased the number of post-menopausal osteoporosis patients. Bone fragility caused by osteoporosis often results in fractures; therefore, ...controlling osteoporosis is crucial to prevent such injuries. To date, various drugs to treat osteoporosis have been developed and launched; however, the molecular mechanisms underlying post-menopausal osteoporosis have not been fully elucidated, and additional factors that could be targeted to treat patients remain to be characterized. Recently, hypoxia inducible factor 1 alpha (HIF1α) was identified as essential for osteoclast activation, an activity that promotes bone loss following menopausal estrogen deficiency. Although osteoclasts, which are located in hypoxic regions of the bone surface, express HIF1α mRNA, in pre-menopausal conditions the presence of estrogen decreases HIF1α protein levels in these cells. In menopausal conditions, however, estrogen deficiency allows HIF1α protein to accumulate in osteoclasts, leading to osteoclast activation and bone loss. Osteoclast-specific conditional HIF1α inactivation protects mice from estrogen deficiency-induced osteoclast activation and bone loss, as does systemic administration of a HIF1α inhibitor. Therefore, HIF1α represents a potential therapeutic target to prevent osteoclast activation and bone loss in post-menopausal patients.
Background:
Previous studies have demonstrated several prognostic factors for retear after arthroscopic rotator cuff repair (ARCR). However, studies that histologically evaluate the quality of the ...torn rotator cuff (RC) tendon and its association with postoperative outcomes are limited.
Purpose:
To investigate factors associated with retear after ARCR using the suture bridge (SB) technique, including the degree of histological degeneration of the RC tendon edge.
Study Design:
Case-control study; Level of evidence, 3.
Methods:
The authors retrospectively evaluated 187 patients who underwent ARCR for full-thickness tears using the SB technique; intraoperative biopsy samples were taken to assess the degree of histological degeneration using the Bonar score. The cohort was divided into healed (n = 165) and retear (n = 22) groups according to magnetic resonance imaging results obtained ≥6 months postoperatively. The evaluation included preoperative patient data (age, sex, symptom duration, trauma history, history of heavy manual work, smoking habit, hypertension, diabetes mellitus, and hyperlipidemia) and radiological data (Hamada classification, Patte classification, Goutallier classification, and global fatty degeneration index GFDI). Additionally, intraoperative data (anteroposterior tear size, Lafosse classification for concomitant subscapularis tendon tear, and long head of biceps injury) and preoperative and postoperative clinical findings (active range of motion, University of California, Los Angeles UCLA, score) were evaluated.
Results:
The retear rate was 11.8%. The retear group had a higher percentage of men (P = .031), higher Bonar score (P < .001), higher mean GFDI value (P = .002), higher rate of tear retraction degree (P = .010), and larger anteroposterior tear size (P = .020) than the healed group. The retear group had lower postoperative internal rotation (P = .031) and lower UCLA score (P < .001). Multivariate logistic regression analysis with a stepwise variable selection revealed anteroposterior tear size (odds ratio OR, 2.4; 95% CI, 1.3-4.5; P = .004) and Bonar score (OR, 1.7; 95% CI, 1.3-2.4; P < .001) as independent predictors for a retear.
Conclusion:
The results indicate that end-stage severe tendon degeneration might affect retear. Therefore, further investigation on the progression mechanisms of tendon degeneration and development of methods to assess degenerative tissue might improve clinical outcomes after ARCR.
Introduction
Osteonecrosis of the jaw (ONJ) occurring after invasive dental treatment often adversely affects patients’ activities of daily living. Long-term administration of strong anti-bone ...resorptive agents such as bisphosphonates prior to invasive dental treatment is considered an ONJ risk factor; however, pathological mechanisms underlying ONJ development remain unclear.
Materials and Methods
We developed an ONJ mouse model in which a tooth is extracted during treatment with the bisphosphonate zoledronate.
Results
We observed induction of apoptosis in osteocytes, resulting in formation of empty lacunae in jaw bones at sites of tooth extraction but not in other bones of the same mice. We also observed elevated levels of inflammatory cytokines such as TNFα, IL-6 and IL-1 in jaw bone at the extraction site relative to other sites in zoledronate-treated mice. We also report that treatment in vitro with either zoledronate or an extract from
Porphyromonas gingivalis
, an oral bacteria, promotes expression of inflammatory cytokines in osteoclast progenitor cells. We demonstrate that gene-targeting of either TNFα, IL-6 or IL-1 or treatment with etanercept, a TNFα inhibitor, or a neutralizing antibody against IL-6 can antagonize ONJ development caused by combined tooth extraction and zoledronate treatment.
Conclusions
Taken together, the cytokine storm induced by invasive dental treatment under bisphosphonate treatment promotes ONJ development due to elevated levels of inflammatory cytokine-producing cells. Our work identifies novel targets potentially useful to prevent ONJ.
It has been well established that an implicit motor response can be elicited by a target perturbation or a visual background motion during a reaching movement. Computational studies have suggested ...that the mechanism of this response is based on the error signal between the efference copy and the actual sensory feedback. If the implicit motor response is based on the efference copy, the motor command accuracy would affect the amount of the modulation of the motor response. Therefore, the purpose of the current study was to investigate the relationship between the implicit motor response and the motor planning accuracy. We used a memory-guided reaching task and a manual following response (MFR) which is induced by visual grating motion. Participants performed reaching movements toward a memorized-target location with a beep cue which was presented 0 or 3 s after the target disappeared (0-s delay and 3-s delay conditions). Leftward or rightward visual grating motion was applied 400 ms after the cue. In addition, an event-related potential (ERP) was recorded during the reaching task, which reflects the motor command accuracy. Our results showed that the N170 ERP amplitude in the parietal electrodes and the MFR amplitude were significantly larger for the 3-s delay condition than the 0-s delay condition. These results suggest that the motor planning accuracy affects the amount of the implicit visuomotor response. Furthermore, there was a significant within-subjects correlation between the MFR and the N170 amplitude, which could corroborate the relationship between the implicit motor response and the motor planning accuracy.
Vitamin D deficiency is a recognized risk factor for sarcopenia development, but mechanisms underlying this outcome are unclear. Here, we show that low vitamin D status worsens immobilization-induced ...muscle atrophy in mice. Mice globally lacking vitamin D receptor (VDR) exhibited more severe muscle atrophy following limb immobilization than controls. Moreover, immobilization-induced muscle atrophy was worse in neural crest-specific than in skeletal muscle-specific VDR-deficient mice. Tnfα expression was significantly higher in immobilized muscle of VDR-deficient relative to control mice, and was significantly elevated in neural crest-specific but not muscle-specific VDR-deficient mice. Furthermore, muscle atrophy induced by limb immobilization in low vitamin D mice was significantly inhibited in Tnfα-deficient mice. We conclude that vitamin D antagonizes immobilization-induced muscle atrophy via VDR expressed in neural crest-derived cells.
Pain is an undesirable sensory experience that can induce depression and limit individuals' activities of daily living, in turn negatively impacting the labor force. Affected people frequently feel ...pain during activity; however, pain is subjective and difficult to judge objectively, particularly during activity. Here, we developed a system to objectively judge pain levels in walking subjects by recording their quantitative electroencephalography (qEEG) and analyzing data by machine learning. To do so, we enrolled 23 patients who had undergone total hip replacement for pain, and recorded their qEEG during a five-minute walk via a wearable device with a single electrode placed over the Fp1 region, based on the 10-20 Electrode Placement System, before and three months after surgery. We also assessed subject hip pain using a numerical rating scale. Brain wave amplitude differed significantly among subjects with different levels of hip pain at frequencies ranging from 1 to 35 Hz. qEEG data were also analyzed by a support vector machine using the Radial Basis Functional Kernel, a function used in machine learning. That approach showed that an individual's hip pain during walking can be recognized and subdivided into pain quartiles with 79.6% recognition Accuracy. Overall, we have devised an objective and non-invasive tool to monitor an individual's pain during walking.
Expectations about forthcoming visual motion shaped by observers' experiences are known to induce anticipatory smooth eye movements (ASEMs) and changes in visual perception. Previous studies have ...demonstrated discrete effects of expectations on the control of ASEM and perception. However, the tasks designed in those studies were not able to segregate the effects of expectations and execution of ASEM itself on perception. In the present study, we attempted to directly examine the effect of ASEM itself on visual speed perception with a two-alternative forced-choice (2AFC) task, in which observers were asked to track a pair of sequentially presented visual motion stimuli with their eyes and to judge whether the second stimulus (test stimulus) was faster or slower than the first (reference stimulus). Our results showed that observers' visual speed perception, quantified by a psychometric function, shifted according to ASEM velocity. This was the case even though there was no difference in the steady-state eye velocity. Further analyses revealed that the observers' perceptual decisions could be explained by a difference in the magnitude of retinal slip velocity in the initial phase of ocular tracking when the reference and test stimuli were presented, rather than in the steady-state phase. Our results provide psychophysical evidence of the importance of initial ocular tracking in visual speed perception and the strong impact of ASEM.
We provide psychophysical evidence that the execution of anticipatory smooth eye movement (ASEM) leads to underestimation of visual speed perception, that is, observers perceive the object motion velocity as slower than when ASEM is not induced, even though the performance of subsequent ocular tracking is comparable. Moreover, our results showed that such perceptual decisions regarding object motion velocity were derived from the ASEM-induced decrease in retinal slip velocity during the initial phase of ocular tracking.
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