Primary extraskeletal osteosarcoma of small bowel mesentery presenting with acute bowel obstruction

Extraskeletal osteosarcoma of the small bowel mesentery is an exceedingly rare condition. It is an aggressive malignant neoplasm of mesenchymal origin characterized by osteoid formation. Final diagnosis is often made by histopathological analysis. However, we believe that prospective radiological diagnosis may be possible through careful analysis of densities (ossification) within the mesenteric mass. To the best of our knowledge, there is no current literature describing the radiological approach to making a prospective diagnosis of this condition. We present the 12th case of extraskeletal osteosarcoma worldwide and describe a radiological approach that is potentially useful in making a prospective diagnosis.

Supplementation of Morin Restores the Altered Bone Histomorphometry in Hyperglycemic Rodents via Regulation of Insulin/IGF-1 Signaling

Pathological mechanisms underlining diabetic bone defects include oxidative damage and insulin/IGF-1 imbalance. Morin is a bioflavonoid with antioxidant and anti-diabetic effects. This study evaluates morin’s protective effects against altered bone histomorphometry in diabetic rats through assessing insulin/IGF-1 pathway as a potential mechanism. Diabetic animals were administered two morin doses (15 and 30 mg/kg) for 5 weeks. Different serum hepatic and renal functions tests were assessed. Bone density and histomorphometry in cortical and trabecular tissues were evaluated histologically. The expressions of insulin, c-peptide and IGF-1 were estimated. In addition, the enzymatic activities of the major antioxidant enzymes were determined. Diabetic-associated alterations in serum glucose, aminotransferases, urea and creatinine were attenuated by morin. Diabetic bone cortical and trabecular histomorphometry were impaired with increased fibrosis, osteoclastic functions, osteoid formation and reduced mineralization, which was reversed by morin; particularly the 30 mg/kg dose. Insulin/IGF-1 levels were diminished in diabetic animals, while morin treatment enhanced their levels significantly. Diabetes also triggered systemic oxidative stress noticeably. The higher dose (30 mg/kg) of morin corrected the endogenous antioxidant enzymatic activities in diabetic rats. Findings indicate the potential value of morin supplementation against hyperglycemia-induced skeletal impairments. Activation of insulin/IGF-1 signaling could be the underlining mechanism behind these effects.

Saponins from the sea cucumber promotes the osteoblast differentiation in MC3T3-E1 cells through activation of BMP2/Smads pathway

Background: Several studies have shown that plant saponins promoted osteoblast differentiation and improved osteoporosis. In current study, sea cucumber saponins (SCS) with a purity of 80% was extracted from Filipino sea cucumber, with a similar structure to plant saponins. Objective: This study aims to investigate the effects of SCS on bone formation in vitro and ex vivo. Results: SCS significantly promoted osteogenic differentiation and mineralization of MC3T3-E1 cells, as well as new osteoid formation in neonatal mouse calvarias ex vivo. qRT-PCR results indicated that SCS markedly down-regulated the expression of C/EBPα* and PPARγ at the levels of transcription, which demonstrate that SCS inhibit the trans-differentiation of MC3T3-E1 cells to an adipocytic phenotype. What is more, further studies revealed that SCS increased the expression levels of Runx2 and OSX. The mechanism revealed that SCS induced the expression of BMP2 and p-Smad1/5, which indicated that SCS facilitated osteogenesis via activating the BMP2/Smads signaling pathway. Conclusion: SCS promoted osteogenic differentiation of pre-osteoblasts by activating BMP2/Smads molecular pathway, providing theoretical basis for the development of sea cucumber saponins for the treatment to bone loss diseases such as osteoporosis.

Cytokeratin-Positive Osteosarcoma Simulating Sarcomatoid Metastatic Carcinoma

Osteosarcoma, the most common primary malignant bone tumor, rarely stains positive for epithelial markers such as cytokeratin on immunohistochemical analysis. We describe a 52-year-old man with a destructive distal femoral metaphyseal lesion who was initially treated for metastatic sarcomatoid carcinoma based on extensive radiographic and histopathologic evaluation. Ultimately, wide resection of the distal femur was performed, revealing high-grade conventional osteosarcoma with intense and diffuse cytokeratin positivity. Such immunohistochemical staining in osteosarcoma is rare, making it difficult to distinguish cytokeratin-positive osteosarcoma from metastatic carcinoma. The presence of a cytokeratin-positive bone neoplasm with malignant osteoid formation on histological studies as well as integration with clinical and radiologic data can help confirm osteosarcoma as the ultimate diagnosis.

Primary Leiomyosarcoma of Bone: Review and Update

Context.— Leiomyosarcoma of bone is a rare primary osseous sarcoma characterized by smooth muscle differentiation and absence of malignant osteoid formation. Leiomyosarcoma of bone is diagnostically challenging; this can be improved with greater awareness of this entity and the ability to differentiate it from its histologic mimics. Because of its rarity, only a small number of studies are available in the literature. These factors contribute to our limited understanding of its pathology, prognosis, and treatment. Objective.— To review the clinicopathologic features of leiomyosarcoma of bone and present the most up-to-date understanding of its behavior and management in accordance with the current literature. Data Sources.— Review of pertinent literature on the major features, current knowledge thereof, and the authors' experience in the diagnosis and management of leiomyosarcoma of bone. Conclusions.— Leiomyosarcoma of bone is a rare but well-recognized primary osseous sarcoma that may arise de novo or in association with radiation. Although it is diagnostically challenging, awareness of this rare sarcoma and knowledge of its key histomorphologic and immunohistochemical features allow for accurate diagnosis.

Petunidin, a B-ring 5′-O-Methylated Derivative of Delphinidin, Stimulates Osteoblastogenesis and Reduces sRANKL-Induced Bone Loss

Several lines of evidence suggest that oxidative stress is one of the key pathogenic mechanisms of osteoporosis. We aimed to elucidate the bone protective effects of petunidin, one of the most common anthocyanidins, considering its potent antioxidative activity. Petunidin (>5 μg/mL) significantly inhibited osteoclastogenesis and downregulated c-fos, Nfatc1, Mmp9, Ctsk, and Dc-stamp mRNA expression in RAW264.7 cells. Conversely, petunidin (>16 μg/mL) stimulated mineralized matrix formation and gene expression of Bmp2 and Ocn, whereas it suppressed Mmp13, Mmp2, and Mmp9 mRNA expression and proteolytic activities of MMP13 and MMP9 in MC3T3-E1 cells. Micro-CT and bone histomorphometry analyses of sRANKL-induced osteopenic C57BL/6J mice showed that daily oral administration of petunidin (7.5 mg/kg/day) increased bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), the ratio of osteoid volume to tissue volume (OV/TV), osteoid thickness (O.Th), the ratio of osteoid surface to bone surface (OS/BS), the ratio of osteoblast surface to bone surface (Ob.S/BS), and the number of osteoblast per unit of bone surface (N.Ob/BS), and decreased trabecular separation (Tb.Sp), the ratio of eroded surface to bone surface (ES/BS), the ratio of osteoclast surface to bone surface (Oc.S/BS), and number of osteoclast per unit of bone surface (N.Oc/BS), compared to untreated mice. Furthermore, histological sections of the femurs showed that oral administration of petunidin to sRANKL-induced osteopenic mice increased the size of osteoblasts located along the bone surface and the volume of osteoid was consistent with the in vitro osteoblast differentiation and MMP inhibition. These results suggest that petunidin is a promising natural agent to improve sRANKL-induced osteopenia in mice through increased osteoid formation, reflecting accelerated osteoblastogenesis, concomitant with suppressed bone resorption.