Fracture healing: micro-computed tomography tells more
Noninvasive characterization of fracture callus structure and composition may facilitate development of surrogate measures of the regain of mechanical function. As such, quantitative computed tomography- (CT-) based analyses of fracture calluses could enable more reliable clinical assessments of bone healing. Although previous studies have used CT to quantify and predict fracture healing, it is unclear which of the many CT-derived metrics of callus structure and composition are the most predictive of callus mechanical properties.
The goal of this study [1] was to identify the changes in fracture callus structure and composition that occur over time and that are most closely related to the regain of mechanical function. Micro-computed tomography (μCT) imaging and torsion testing were performed on murine fracture calluses (n=188) at multiple postfracture timepoints and under different experimental conditions that alter fracture healing. Total callus volume (TV), mineralized callus volume (BV), callus mineralized volume fraction (BV/TV), bone mineral content (BMC), tissue mineral density (TMD), standard deviation of mineral density (σTMD), effective polar moment of inertia (Jeff), torsional strength, and torsional rigidity were quantified. Multivariate statistical analyses were used to identify differences in callus structure and composition among experimental groups, and to determine which of the μCT outcome measures were the strongest predictors of mechanical properties.
RANKL inhibition with osteoprotegerin increases bone strength in ovariectomized rats
Ovariectomy results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. The purpose of a recent study [1] was to examine whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in ovariectomized rats. Rats were ovariectomized or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle. Ovariectomized rats were treated with vehicle or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b, an osteoclast marker, was measured by ELISA. BMD of lumbar vertebrae (L1–L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by µCT and biomechanical testing, and L6 was analyzed for ash weight.
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Stem cells: a promising target to enhance bone regeneration
Mesenchymal stem/progenitor cells (MSCs) can differentiate into adipocytes, muscle cells, osteoblasts, or cartilage and possess potential for tissue repair in patients with osteoporosis, diseased joints, and myocardial infarction. Many groups have investigated strategies involving the infusion of MSCs for the purpose of regenerative therapy; however, problems concerning MSC homing to diseased sites and the use of allogeneic MSCs have limited this approach. Therefore, the ability to use pharmacological agents to induce the differentiation of resident MSCs toward a certain lineage in vivo is an important therapeutic goal. In a recent study [1], the authors report that bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of MSCs into osteoblasts, resulting in new bone formation.
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Thyroid-stimulating hormone prevents ovariectomy-induced bone loss
Clinical data evidence the strong correlation between fracture risk and serum thyroid-stimulating hormone (TSH). Recent evidence that TSH receptor polymorphisms are associated with low bone mass, and evidence that bone loss occurs in patients with subclinical hyperthyroidism with normal and low TSH levels all support a role for low TSH in the pathogenesis of hyperthyroid osteoporosis, hitherto attributed solely to high circulating levels of thyroid hormones. In mice, TSH receptor deficiency induces a high-turnover osteoporosis, with elevated bone formation and resorption. In cell cultures continually exposed to TSH, both osteoblastic bone formation and osteoclastic bone resorption were suppressed. Recent studies on both mice and human subjects provide compelling evidence that thyroid hormones and TSH have the opposite effects on the skeleton.
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Osteocalcin differentially regulates ß-cell and adipocyte gene expression and affects the development of metabolic diseases in mice
The osteoblast-specific secreted molecule osteocalcin behaves as a hormone regulating glucose metabolism and fat mass in two mutant mouse strains [1]. In a recent study [2], the authors asked two questions: is the action of osteocalcin on β-cells and adipocytes elicited by the same concentrations of the molecule, and more importantly, does osteocalcin regulate energy metabolism in wild-type mice? Cell-based assays using isolated pancreatic islets, a β-cell line, and primary adipocytes showed that picomolar amounts of osteocalcin are sufficient to regulate the expression of the insulin genes and β-celll proliferation markers, whereas nanomolar amounts affect adiponectin and Pgc1α expression in white and brown adipocytes, respectively.
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 Download here the slide set presented by Prof. Friedlander, on Thursday, March 29th. |
