Mouse shoulder morphology responds to locomotor activity and the kinematic differences of climbing and running.

Mechanical loads play a significant role in determining long bone shape and strength, but less work has explored how these loads influence flat bones like the scapula, which has been shown to vary with locomotor preference among primate taxa. Here, we tested the effects of voluntary running and climbing exercise in mice to examine how the mechanical loads borne from different locomotor patterns influence shoulder morphological development. Ninety-nine female wild-type mice were distributed equally among sedentary control, activity-wheel running, and vertical climbing experimental conditions. Running mice had the lowest body masses, larger intrinsic shoulder muscles, and the most pronounced differences in scapular size and shape relative to the other groups. Climbing mouse scapular morphology also differed significantly from the control individuals, but these differences were not as marked as those between the running and control mice. This might be attributable in part to greater levels of activity in the wheel-runners relative to the climbers. Additionally, climbing mice held their bodies closer to the substrate and maintained more flexed limbs and posterior hand positions compared with the kinematics of running. As a result, climbers differed significantly from both the running and control mice in developing a relatively broader infraspinous region, which is likely related to preferential recruitment of the infraspinatus and teres minor muscles to maintain flexed shoulder postures. The results of this study demonstrate that variation in activity level and type of locomotor regime over a significant portion of the life history influences muscle and bone development in the shoulder.

Osteosarcoma cells differentiate into phenotypes from all three dermal layers.

BACKGROUND: Osteosarcomas are the most common solid malignant bone tumors, but little is known of their origin. The embryonal rest hypothesis views cancer cells as arising from committed progenitor stem cells in each tissue. Adult tissue contains primitive stem cells that retain the ability to differentiate across dermal lines, raising the possibility that the stem cell of origin of cancers may be from a more primitive stem cell than a progenitor. QUESTIONS/PURPOSES: Can osteosarcoma cells, when cultured under conditions used for multipotent stem cells, be induced to differentiate into multiple phenotypes, including those of the three different dermal lineages: mesodermal, ectodermal, and endodermal? METHODS: One rat and one human osteosarcoma cell line were cultured and treated with concentrations of 0, 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L dexamethasone for 5 weeks. Seventeen phenotypes were assayed either by tissue-specific histochemical stains or antibodies to tissue-specific proteins. Each phenotype was tested across all dexamethasone concentrations for each cell line and each phenotype was tested in three separate experiments with induction by dexamethasone RESULTS: Rat osteosarcoma (ROS) 17/2.8 and human osteosarcoma cell line U-2 show the appearance of cells that have markers for (1) mesodermal phenotypes such as bone, cartilage, skeletal muscle, and endothelial cells, (2) ectodermal phenotypes such as astrocytes, oligodendrocytes, neurons, and keratinocytes, and (3) an endodermal phenotype, hepatocytes. This indicates osteosarcomas are composed, at least in part, of primitive stem cells capable of differentiating into tissues from all three dermal lineages. CLINICAL RELEVANCE: If osteosarcomas arise from primitive stem cells, then treatment of osteosarcomas with exogenous differentiation agents may cause the stem cells to differentiate, thus halting their proliferation and stopping tumor growth.