Sclerostin Antibody Augments the Anabolic Bone Formation Response in a Mouse Model of Mechanical Tibial Loading

Decreased activity or expression of sclerostin, an endogenous inhibitor of Wnt/β-catenin signaling, results in increased bone formation and mass. Antibodies targeting and neutralizing sclerostin (Scl-Ab) have been shown to increase bone mass and reduce fracture risk. Sclerostin is also important in modulating the response of bone to changes in its biomechanical environment. However, the effects of Scl-Ab on mechanotransduction are unclear, and it was speculated that the loading response may be altered for individuals receiving Scl-Ab therapy.

Heterozygous deletion of both sclerostin (Sost) and connexin43 (Gja1) genes in mice is not sufficient to impair cortical bone modeling

Connexin43 (Cx43) is the main gap junction protein expressed in bone forming cells, where it modulates peak bone mass acquisition and cortical modeling. Genetic ablation of the Cx43 gene (Gja1) results in cortical expansion with accentuated periosteal bone formation associated with decreased expression of the Wnt inhibitor sclerostin.

Combination of PTH (1-34) with anti-IL17 prevents bone loss by inhibiting IL-17/N-cadherin mediated disruption of PTHR1/LRP-6 interaction

Combinations of anabolic and anti-resorptive agents have potential to improve bone density more than either agent alone. In this study, we determine the combining effect of anti-IL17 antibody and PTH (1-34) in mitigation of ovariectomy induced bone loss. Ovariectomized BALB/c female mice were treated with anti-IL17 and iPTH monotherapies and their combination.

Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons

The small leucine-rich proteoglycans (SLRPs), decorin and biglycan, are key regulators of collagen fibril and matrix assembly. The goal of this work was to elucidate the roles of decorin and biglycan in tendon homeostasis. Our central hypothesis is that decorin and biglycan expression in the mature tendon would be critical for the maintenance of the structural and mechanical properties of healthy tendons.

Improving Combination Osteoporosis Therapy in a Preclinical Model of Heightened Osteoanabolism

Combining anticatabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Toward the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 because disabling this gene amplifies PTH-induced increases in trabecular bone in mice by boosting osteoblast secretory activity.

Hibernating Little Pocket Mice Show Few Seasonal Changes in Bone Properties

Periods of disuse or physical inactivity increases bone porosity and decreases bone mineral density, resulting in a loss of bone mechanical competence in many animals. Although large hibernators like bears and marmots prevent bone loss during hibernation, despite long periods of physical inactivity, some small hibernators do lose bone during hibernation.