[Treatment of proximal humeral fractures with proximal humeral locking system plate via an intertubercular sulcus approach].

OBJECTIVE: To observe the effect of proximal humerus internal locking system (PHILOS) plate in the treatment of Neer 2 and 3 part fractures of proximal humerus through tuberosity approach. METHODS: From July 2015 to January 2018, 15 cases of proximal humerus Neer 2 and 3 fractures were treated with PHILOS plate through intertubercular sulcus approach. There were 7 males and 8 females. The age ranged from 23 to 67 years old, with an average of 46 years old. There were 5 cases on the left side and 10 cases on the right side (including 7 cases of Neer 2 partial fracture and 8 cases of Neer 3 partial fracture). X-ray films and CT were taken before and after operation to assess fracture location and fracture healing. Clinical evaluation included Constant-Murley shoulder function score and operative complications. All 15 patients were treated with the PHILOS. Constant-Murley score was used to evaluate shoulder function after operation. RESULTS: All the 15 cases were followed up, and the duration ranged from 14 to 36 months. All the fractures healed and the healing time ranged from 14 to 26 weeks, averaged 19.1 weeks. There were no complications such as humeral head necrosis, axillary nerve injury and fracture nonunion after operation. At the 3rd month after operation, the shoulder function score of Constant-Murley ranged from 72 to 94 points, with an average of 81 points; 2 cases got an excellent result and 13 good. CONCLUSIONS: The PHILOS plate for the treatment of proximal humerus fractures has the advantages of simple operation, small injury and quick recovery of shoulder joint function.

Tetrandrine induces apoptosis and triggers a caspase cascade in U2-OS and MG-63 cells through the intrinsic and extrinsic pathways.

Although neoadjuvant chemotherapy has improved the survival rate of osteosarcoma patients, drug resistance remains a predominant obstacle to improving efficacy and necessitates the development of novel chemotherapeutical agents. The aim of this study was to investigate whether tetrandrine (TET) induces apoptosis in the U-2OS and MG-63 osteosarcoma cell lines and to further determine the underlying mechanism. This study investigated the effects of TET on osteosarcoma in vitro. To examine the antitumor effects of TET on osteosarcoma, the two osteosarcoma cell lines were treated with TET and subjected to apoptosis assays. The results revealed that TET induced the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Furthermore, the apoptosis of osteosarcoma cells was accompanied by increased cytochrome c (Cyto-C), apoptotic protease-activating factor (Apaf)-1, Bid and Bax activation and reduced Bcl-2 and Bcl-xl activation, demonstrating that the apoptosis may have occurred through the mitochondrial pathway. In conclusion, the results suggest that TET is a promising agent for osteosarcoma therapy.

Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.

Gambogic acid (GA), the natural product, has been demonstrated to be a promising chemotherapeutic drug for osteosarcoma (OS) due to its ability to induce apoptosis and cell cycle arrest. To date, no studies have examined the role of GA in metastatic bone disease. Matrix metalloproteinases (MMPs) play critical roles in invasion and metastasis, and the tissue inhibitors of metalloproteinase (TIMP) family regulates the activity of multifunctional metalloproteinases. In this study, we investigated the gene expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in OS cell lines treated by the GA. The expression of MMP-9 and TIMP-1 were studied by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. In vitro invasion of OS cell lines (Saos-2, MG-63) were investigated by the Matrigel invasion assay. Mean MMP-9 protein and mRNA expression was significantly suppressed; in addition, mean TIMP-1 protein mRNA expression were upregulated by increasing GA concentrations. GA reduced the invasiveness of OS cell lines dose-dependently. Furthermore, specific inhibition of TIMP-1 secretion with siRNA against TIMP-1 significantly reduced the effect of GA on OS cell lines. Overall, our findings suggest that GA reduces the invasive potential of OS cells via attenuation of MMP-9 and upregulation of TIMP-1. Moreover, TIMP-1 played an important role in the reduction of invasive potential of the OS cells which were treated by GA.

Elevated local TGF-ß1 level predisposes a closed bone fracture to tuberculosis infection.

Tuberculosis (TB) occurring after a closed bone fracture in the patient with no history of TB and no evidence of TB infection at the time of initial fracture is a rare entity. Transforming growth factor-beta 1 (TGF-ß1) is a ubiquitous growth factor that is implicated in the regulation of the proliferation, differentiation, migration, and survival of many different cell types. Recent studies have demonstrated that the local level of TGF-ß1 in bone is significantly elevated during fracture healing and TGF-ß1 plays an important role in TB progression. Given the above background, we hypothesize that elevated local TGF-ß1 level predisposes a closed bone fracture to TB infection. This was supported by conclusions drawn from literature reviews: (1) the local level of TGF-ß1 in bone is significantly elevated during fracture healing; (2) TGF-ß1 inhibits T lymphocyte activation; (3) TGF-ß1 is a potent macrophage-deactivating molecule; (4) TGF-ß1 suppresses the production and activity of some proinflammatory cytokines.

Decreases in fluid shear stress due to microcracks: a possible primary pathogenesis of Kümmell's disease.

The German doctor Hermann Kümmell described Kümmell's disease as the clinical scenario in which patients suffer a trivial spinal trauma, but develop a symptomatic, progressive, angular kyphosis after a symptom-free period of months to years. Since an intravertebral vacuum phenomenon, which is considered indicative of ischemic osteonecrosis, is often seen in the radiographs of patients with Kümmell's disease, most authors regard ischemic necrosis of the vertebral body as the primary pathogenesis of Kümmell's disease. However, we argue that Kümmell's disease is not commonly associated with typical avascular osteonecrosis of the femoral head and the intravertebral vacuum phenomenon is also present in other diseases. We postulated that even if ischemia plays a role in the pathogenesis of Kümmell's disease, it would not be the proximal cause of Kümmell's disease. In this article, we review the role of fluid shear stress in bone remolding and propose a microcosmic hypothesis in which microcracks lead to decreased fluid shear stress, which acts as the primary cause of Kümmell's disease. This was supported by conclusions drawn from a literature review: (1) fluid shear stress plays a crucial role in bone remodeling, and the osteocyte network is the main sensor of this mechanical stimulus; (2) decreased fluid shear stress will cause disequilibration of bone homeostasis, increasing bone resorption and reducing bone formation; and (3) the fluid flow of lacunar-canalicular porosity (PLC) and fluid shear stress near the microcracks decreases.