No abstract

No abstract

Mechanical unloading simultaneously induces muscle and bone loss, but its mechanisms are not fully understood. The interactions between skeletal muscle and bone have been recently noted. Although canonical wingless-related integration site (Wnt)/β-catenin signaling is crucial for bone metabolism, its roles in the muscle and bone interactions have remained unknown. Here, we performed comprehensive DNA microarray analyses to clarify humoral factors linking muscle to bone in response to mechanical unloading and hypergravity with 3 g in mice. We identified Dickkopf (Dkk) 2, a Wnt/β-catenin signaling inhibitor, as a gene whose expression was increased by hindlimb unloading (HU) and reduced by hypergravity in the soleus muscle of mice. HU significantly elevated serum Dkk2 levels and Dkk2 mRNA levels in the soleus muscle of mice whereas hypergravity significantly decreased those Dkk2 levels. In the simple regression analyses, serum Dkk2 levels were negatively and positively related to trabecular bone mineral density and mRNA levels of receptor activator of nuclear factor-kappa B ligand (RANKL) in the tibia of mice, respectively. Moreover, shear stress significantly suppressed Dkk2 mRNA levels in C2C12 cells, and cyclooxygenase inhibitors significantly antagonized the effects of shear stress on Dkk2 expression. On the other hand, Dkk2 suppressed the mRNA levels of osteogenic genes, alkaline phosphatase activity and mineralization, and it increased RANKL mRNA levels in mouse osteoblasts. In conclusion, we showed that muscle and serum Dkk2 levels are positively and negatively regulated during mechanical unloading and hypergravity in mice, respectively. An increase in Dkk2 expression in the skeletal muscle might contribute to disuse- and microgravity-induced bone and muscle loss.

The number of elderly patients with sarcoma (65 years or older) has increased with the rise in the aging of society. As it is difficult to treat elderly sarcoma patients in the same manner as younger patients, the present study sought to compare treatment options currently available for elderly patients. The present study was comprised 34 Japanese patients (21 men and 13 women) with malignant bone or soft tissue tumors who underwent surgery in our department from September 2004 to March 2014. The median patient age was 72 years (range, 65-86 years). Histologically, 23 cases were categorized as high-grade and 11 as low-grade. Treatments included surgery with adequate margins (25 cases), surgery with inadequate margins and radiotherapy (4 cases), surgery with inadequate margins and chemotherapy (3 cases) and intralesional resection (2 cases). The postoperative follow-up period ranged from 7 to 112 months (average, 49 months). The 5-year survival rates were determined and compared using the Kaplan-Meier method and log-rank test, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and Anesthesiologists-Physical Status (ASA-PS) scores were also determined. The overall 5-year survival rate was 86.02%; it differed significantly between patients with high-grade (100%) vs. low-grade (74.3%) neoplasms P<0.001), but not between patients aged 65-69 (76.9%) vs. ≥70 (90.2%) years-old (P=0.65). Tumor status was classified as follows: i) Continuously disease-free, n=24 cases; ii) alive with disease, n=3 cases; iii) and dead of disease, n=7 cases. The ECOG-PS status scores were 0 in 9 cases, 1 in 21 cases, and 2 in 4 cases. ASA-PS scores were also I in 9 cases and II in 23 cases. Thus, the primary treatment for elderly patients with sarcoma should be surgery alone as no additional benefits were obtained when radiotherapy or chemotherapy was also performed. Adequate margins should be confirmed along with the histology of surgical specimens.

Low-grade fibromyxoid sarcoma is a slowly growing soft tissue neoplasm, mostly affecting young individuals. It usually arises in a deep soft tissue of the lower limbs and trunk, but few cases of low-grade fibromyxoid sarcoma that presents sciatic nerve pain have been reported. We report a 34-year-old woman with a low-grade fibromyxoid sarcoma originating in the left gluteal region that initially presented as sciatic nerve pain; she had experienced this type of pain for 5 years before visiting our hospital. Magnetic resonance imaging revealed a tumor in the left gluteal region. After needle biopsy revealed it to be a low-grade fibromyxoid sarcoma, we performed the wide resection. Intra-operative findings revealed no tumor invasion into the sciatic nerve. No recurrence or metastasis has been detected 6 months post-surgery. Oncologists who encounter patients with sciatic nerve pain should consider the possibility of less common causes such as the low-grade fibromyxoid sarcoma found in our patient.