Mechanical loading inhibits bone resorption: osteocytes are the sensors
Bone adjusts its structure to become better suited to withstand the mechanical demands it experiences. Physical loading and routine activities have been shown to inhibit bone resorption. However, the cellular mechanism underlying this phenomenon remains largely unknown. The focus of a recent study [1] was to determine the mechanisms by which osteocytes might transduce and regulate bone resorption, and the antiresorptive effects of loading.
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The future of bone formation: pharmacological manipulation of the Wnt signaling pathway
One pathway identified by human genetics as a major player in the control of bone formation is the Wnt signaling pathway [1]. This pathway is crucial for the specification of cell fates, regulation of cell growth, differentiation, and apoptosis. Wnt ligands are secreted lipid-modified glycoproteins that signal through a receptor complex comprising a member of the Frizzled family of seven transmembrane domain receptors, and the co-receptor lipoprotein-receptor related proteins (LRPs) 5 or 6.
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Associations between the metabolic syndrome and bone health in older men and women
Metabolic syndrome is defined as a cluster of risk factors that are associated with diabetes, central obesity, and increased risk of cardiovascular disease. The 2001 National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) definition requires the presence of at least 3 of 5 of the following categorically defined risk factors: abdominal obesity (waist circumference greater than 102 cm in men or greater than 88 cm in women), high triglycerides (150 mg/dl or greater), low HDL cholesterol (less than 40 mg/dL in men or less than 50 mg/dL in women), hypertension (130/85 mm Hg or greater), and hyperglycemia (110 mg/dL or greater). Metabolic syndrome is associated with cardiovascular disease morbidity. The association between each of these risk factors and osteoporosis has been previouly studied, with contradictory results. A recent study [1] used multivariate regression models to examine the cross-sectional associations of MS defined by NCEP-ATP III criteria with bone mineral density (BMD) and osteoporosis, and the longitudinal association of MS with fractures in 420 men and 676 women from the Rancho Bernardo Study.
The effect of leptin on bone mineral density: young men too…
Osteoporosis-related fractures constitute a major public health concern in women and men, and the fracture risk is highly dependent on bone mineral density (BMD). Although it is well established that obesity is a major risk factor for several common and severe diseases, the link between obesity and osteoporosis is less clear. A large body of evidence supports the notion that body weight is positively associated with areal BMD (aBMD) in both sexes and at all ages throughout adulthood, and negatively associated with fracture incidence. However, it remains a controversy whether it is lean mass or adipose tissue that mediates the bone stimulatory effect exerted by weight.
Osteocytes are crucial actors in mechanotransduction
The role of osteocytes in bone is still an enigma. It was thought that osteocytes are passive cells or ¿¿placeholders¿¿ in bone or, conversely, that osteocytes could potentially be mechanosensors and transducers of mechanical load. A new study [1] now sheds light on the role of osteocytes in maintaining skeletal homeostasis and regulating skeletal responses to mechanical loading. Loading, as occurs with exercise, increases bone mass. Conversely, unloading, as occurs with space flight or immobilization, results in bone loss. The complex lacunocanalicular network connecting all of the osteocytes within bone and cells on the bone surface supports the idea that these cells can sense loading on the skeleton or its absence and then translate those signals to biochemical signals of resorption or formation. The authors used an ingenious approach to determine the role of osteocytes by loss-of-function studies. Using mice carrying a diphtheria toxin (DT) receptor specifically expressed in osteocytes, the authors were able to kill off osteocytes using single injections of DT.
 Download here the slide set presented by Prof. Friedlander, on Thursday, March 29th. |
