Fluid-solid coupling numerical simulation of trabecular bone under cyclic loading in different directions.

The structure of a bone tissue is capable of adapting to mechanical loading through the process of bone remodeling, which is regulated by osteoblasts and osteoclasts. Fluid flow within trabecular porosity under cyclic loading is one of the factors stimulating the biological response of osteoblasts and osteoclasts. However, the relation between loading directions and interstitial fluid flow was seldom studied. In the present study, a finite element model based on micro-computed tomographic reconstructions is built by using a mouse femur. Results from the fluid-solid coupling numerical simulation indicate that the loading in different directions generates a distinct distribution of von Mises stress in the bone matrix and a fluid shear stress (FSS) in the bone marrow. The loading along the physiological direction leads to a more uniform distribution of solid stress and produces an FSS level beneficial to the biological response of osteoblasts and osteoclasts compared with those along the non-physiological direction. There was a minimum threshold line of wall FSS with a specific solid stress at the bone surface, suggesting that the wall FSS is mainly induced by the solid strain. These results may offer fundamental data in understanding the mechanical environment around osteoblasts and osteoclasts and the cellular and molecular mechanisms of mechanical loading-induced bone remodeling.

Stem cells from human exfoliated deciduous teeth ameliorate concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis.

BACKGROUND: Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities. AIM: To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms. METHODS: We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms. RESULTS: SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+, CD4+, tumor necrosis-alpha+, and interferon-gamma+ inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis. CONCLUSION: SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.