Role of peripheral myelin protein 22 in chronic exercise-induced interactions of muscle and bone in mice.

Exercise is important for the prevention and treatment of sarcopenia and osteoporosis. Although the interactions between skeletal muscles and bone have recently been reported, the myokines linking muscle to bone during exercise remain unknown. We previously revealed that chronic exercise using treadmill running blunts ovariectomy-induced osteopenia in mice. We herein performed an RNA sequence analysis of the gastrocnemius and soleus muscles of male mice with or without chronic exercise to identify the myokines responsible for the effects of chronic exercise on the muscle/bone relationship. We extracted peripheral myelin protein 22 (PMP22) as a humoral factor that was putatively induced by chronic exercise in the soleus and gastrocnemius muscles of mice from the RNA sequence analysis. Chronic exercise significantly enhanced the expression of PMP22 in the gastrocnemius and soleus muscles of female mice. PMP22 suppressed macrophage-colony stimulating factor and receptor activator factor κB ligand-induced increases in the expression of osteoclast-related genes and osteoclast formation from mouse bone marrow cells. Moreover, PMP22 significantly inhibited osteoblast differentiation, alkaline phosphatase activity, and mineralization in mouse osteoblast cultures; however, the overexpression of PMP22 did not affect muscle phenotypes in mouse muscle C2C12 cells. A simple regression analysis revealed that PMP22 mRNA levels in the gastrocnemius and soleus muscles were positively related to cortical bone mineral density at the femurs of mice with or without chronic exercise. In conclusion, we identified PMP22 as a novel myokine induced by chronic exercise in mice. We first showed that PMP22 suppresses osteoclast formation and the osteoblast phenotype in vitro.

Is physical capacity correlated with health-related quality of life in patients with adolescent idiopathic scoliosis?

BACKGROUND: There have been no report about the association between physical capacity and health-related quality of life in patients with adolescent idiopathic structural scoliosis (AIS). This study aims to investigate the correlation between dynamic cardiopulmonary capacity and quality of life in AIS patients. METHODS: This retrospective study involved 63 patients. Correlations between cardiopulmonary exercise test parameters and Scoliosis Research Society (SRS)-22 scores were evaluated using Spearman's correlation test. RESULTS: Fifty-four female patients [mean age: 14.1 (range, 10-19) years] and 9 male patients [15.9 (range, 14-19) years] with AIS (Cobb angle: 28°-86°) were included. Significant correlations were found between the peak oxygen uptake normalized by body weight and the SRS-22 scores in female patients, as reflected by the function (r=0.511, P<0.001), pain (r=0.418, P=0.002), mental health (r=0.536, P<0.001) and subtotal (r=0.618, P<0.001) scores. Significant correlations were also found between oxygen uptake at anaerobic threshold normalized by body weight and the SRS-22 scores in female patients, as reflected by the function (r=0.404, P=0.002), pain (r=0.455, P=0.001), and subtotal (r=0.501, P<0.001) scores, along with respiratory exchange ratio reflected by subtotal (r=0.464, P<0.001) score. CONCLUSIONS: The physical capacity and capacity for the exercise intensity and endurance correlated with quality of life among patients with AIS. Exercise may better the quality of life of patients with AIS.

Adaptation to reduced lung function in children and young people with spinal deformity.

BACKGROUND: Severe scoliosis can affect respiratory function in growing patients and produce cardiopulmonary complications, leading to significant morbidity. The development of spinal deformity may impact on young patients' level of function and reported quality of life (QOL). The aim of this study was to investigate the relationship between lung function, exercise capacity and quality of life in young patients with spinal deformity. METHODS: This is a retrospective analysis of 104 patients (31% male, 69% female with mean age 14.9yrs). 77% of patients had an adolescent idiopathic scoliosis, with the remainder having other scoliosis diagnoses or Scheuermann's kyphosis. Principal outcomes included Spirometry [FEV1, FVC], Whole Body Plethysmography, Cardiopulmonary Exercise Testing [CPET] and patient outcome questionnaires (with SRS-22). CPET measures included maximal exercise capacity [VO2peak] as well as VO2 at ventilatory threshold [VT] expressed as %predicted VO2max-a measure of physical conditioning, and minute ventilation [VE] from which breathing reserve [BR] could be calculated. RESULTS: Mean (±SD) main thoracic scoliosis was 59.9° (±15.2°), and mean kyphosis in those with Scheuermann's condition was 95.3° (±11.5°). No correlation was elicited between FEV1 or FVC (%predicted) and VO2peak (%predicted) in this patient cohort. Greater thoracic curves were associated with lower FEV1 (%predicted), r = -0.343, p = 0.001, FVC (%predicted), r = -0.307, p = 0.003 and BR (%) at the end of exercise (r = -0.-0.459, p < 0.001). The patient cohort had a mean (sd) VO2peak of 98(17) %predicted, with greater VO2peak levels recorded in female subjects, those of younger age and those with higher scoliosis angles. Those with better lung function [FEV1 (%predicted)] had better BR (%) at the end of exercise (r = 0.483, p < 0.001). SRS-22 scores correlated significantly with VO2peak (%predicted) (total SRS-22 versus VO2peak (%predicted), r = 0.336, p = 0.002). CONCLUSION: Larger thoracic scoliotic curves are associated with poorer lung function but better exercise capacity, likely related to higher levels of physical conditioning. Higher QOL scores were recorded in patients who had greater VO2peak levels, suggesting that exercise capacity may be a protective factor for emotional well-being in patients with spinal deformity.

The Effects of Ergosta-7,9(11),22-trien-3ß-ol from Antrodia camphorata on the Biochemical Profile and Exercise Performance of Mice.

Antrodia camphorata (AC) is a rare and unique mushroom that is difficult to cultivate. Previous studies have demonstrated the bioactivity of the compound Ergosta-7,9(11),22-trien-3ß-ol (EK100) from AC in submerged culture. The purpose of this study is to evaluate the potential beneficial effects of EK100 on fatigue and ergogenic functions following physiological challenge. Male ICR (Institute of Cancer Research) mice were randomly divided into three groups (n = 8 per group) and orally administered EK100 for six weeks at 0 (Vehicle), 10 (EK100-1X), and 20 (EK100-2X) mg/kg/day. The six-week Ek100 supplementation significantly increased grip strength (P = 0.0051) in trend analysis. Anti-fatigue activity was evaluated using 15-min. acute exercise testing and measuring the levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) after a 15-min. swimming exercise. Our results indicate that AC supplementation leads to a dose-dependent decrease in serum lactate, ammonia, BUN, and CK activity after exercise and significantly increases serum glucose and glycogen content in liver tissues. Biochemical and histopathological data demonstrated that long term daily administration of EK100 for over six weeks (subacute toxicity) was safe. EK100's anti-fatigue properties appear to be through the preservation of energy storage, increasing blood glucose and liver glycogen content, and decreasing the serum levels of lactate, ammonia, BUN, and CK. EK100 could potentially be used to improve exercise physiological adaptation, promote health, and as a potential ergogenic aid in combination with different nutrient strategies.

URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia.

BACKGROUND: Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid (UA) reabsorption in the proximal tubule, is caused by mutations in SLC22A12 or SLC2A9. Most mutations have been identified in Japanese patients, and only a few have been detected in Europeans. METHODS: We report clinical, biochemical and genetics findings of fourteen Spanish patients, six Caucasians and eight of Roma ethnia, diagnosed with idiopathic RHUC. Two of the patients presented exercise-induced acute renal failure and another one had several episodes of nephrolithiasis and four of them had progressive deterioration of renal function, while the rest were asymptomatic. RESULTS: Molecular analysis revealed SLC22A12 mutations in ten of the patients, and SLC2A9 mutations in the other four. A new heterozygous SLC22A12 missense mutation, c.1427C>A (p.A476D), was identified in two affected members of the same family. The rest of the patients presented homozygous, heterozygous or compound heterozygous mutations that have been previously identified in patients with RHUC; SLC22A12 p.T467M and p.L415_G417del, and SLC2A9 p.T125M. Expression studies in Xenopus oocytes revealed that c.1427C>A reduced UA transport but did not alter the location of URAT1 protein on the plasma membrane. CONCLUSIONS: The biochemical and clinical features of our patients together with the genetic analysis results confirmed the diagnosis of RHUC. This is the first report describing SLC22A12 and SLC2A9 mutations in Spanish patients.

Identification of CaV channel types expressed in muscle afferent neurons.

Cardiovascular adjustments to exercise are partially mediated by group III/IV (small to medium) muscle afferents comprising the exercise pressor reflex (EPR). However, this reflex can be inappropriately activated in disease states (e.g., peripheral vascular disease), leading to increased risk of myocardial infarction. Here we investigate the voltage-dependent calcium (CaV) channels expressed in small to medium muscle afferent neurons as a first step toward determining their potential role in controlling the EPR. Using specific blockers and 5 mM Ba(2+) as the charge carrier, we found the major calcium channel types to be CaV2.2 (N-type) > CaV2.1 (P/Q-type) > CaV1.2 (L-type). Surprisingly, the CaV2.3 channel (R-type) blocker SNX482 was without effect. However, R-type currents are more prominent when recorded in Ca(2+) (Liang and Elmslie 2001). We reexamined the channel types using 10 mM Ca(2+) as the charge carrier, but results were similar to those in Ba(2+). SNX482 was without effect even though ∼27% of the current was blocker insensitive. Using multiple methods, we demonstrate that CaV2.3 channels are functionally expressed in muscle afferent neurons. Finally, ATP is an important modulator of the EPR, and we examined the effect on CaV currents. ATP reduced CaV current primarily via G protein ßγ-mediated inhibition of CaV2.2 channels. We conclude that small to medium muscle afferent neurons primarily express CaV2.2 > CaV2.1 ≥ CaV2.3 > CaV1.2 channels. As with chronic pain, CaV2.2 channel blockers may be useful in controlling inappropriate activation of the EPR.

A case of renal hypouricemia and a G774A gene mutation causing acute renal injury that was improved by hemodialysis.

A 16-year-old man came to our hospital complaining of loin pain after a middle-distance race. Following admission, his renal dysfunction worsened rapidly, requiring several hemodialysis sessions. A renal biopsy showed no change in the glomeruli, although interstitial edema was observed. Following the recovery of renal function, we confirmed that his uric acid level was abnormally low and urate clearance was abnormality high. Gene analysis showed that he had a G774A mutation which dominated the SLC22A12 gene encoding the urate transporter 1.