Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes

Background Neutralising antibodies to sclerostin (Scl-Ab) have shown significant potential to induce bone formation and decrease bone resorption, increase strength and substantially reduce fracture risk in animal studies and clinical trials. Mechanical loading negatively regulates sclerostin expression, and sclerostin has been shown to induce RANKL synthesis in osteocytes. However, how Scl-Ab governs osteocyte regulation of osteoclast differentiation and function is not fully understood. We have recently discovered that osteoblasts and osteocytes alter osteoclastogenic signalling (RANKL/OPG) during estrogen-deficiency, and that osteoblast-induced osteoclastogenesis and resorption are exacerbated. However, it is not known whether estrogen deficient osteocytes exacerbate osteoclastogenesis. The aims of this study were to (1) establish whether osteocytes induce osteoclastogenesis and bone resorption during estrogen deficiency in vitro (2) investigate whether the sclerostin antibody can revert osteocyte-mediated osteoclastogenesis and resorption by attenuating RANKL/OPG expression. Results Using conditioned media and co-culture experiments we found increased osteocyte-induced osteoclastogenesis and bone resorption in estrogen deficient conditions. This is the first study to report that administration of Scl-Ab has the ability to revert osteocyte-mediated osteoclastogenesis and resorption by decreasing RANKL/OPG ratio expression and increasing WISP1 expression in estrogen deficient osteocytes. Conclusions This study provides an enhanced understanding of the biological changes underpinning decreases in bone resorption following Scl-Ab treatment observed in vivo by revealing that Scl-Ab can reduce pro-osteoclastogenic cell signalling between osteocytes and osteoclasts.

Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes

Neutralising antibodies to sclerostin (Scl-Ab) have shown significant potential to induce bone formation and decrease bone resorption, increase strength and substantially reduce fracture risk in animal studies and clinical trials. Mechanical loading negatively regulates sclerostin expression, and sclerostin has been shown to induce RANKL synthesis in osteocytes. However, how Scl-Ab governs osteocyte regulation of osteoclast differentiation and function is not fully understood. We have recently discovered that osteoblasts and osteocytes alter osteoclastogenic signalling (RANKL/OPG) during estrogen-deficiency, and that osteoblast-induced osteoclastogenesis and resorption are exacerbated. However, it is not known whether estrogen deficient osteocytes exhibit exacerbate osteoclastogenesis. The aims of this study were to (1) establish whether osteocytes induce osteoclastogenesis and bone resorption during estrogen deficiency in vitro (2) investigate whether the sclerostin antibody can revert osteocyte-mediated osteoclastogenesis and resorption by attenuating RANKL/OPG expression.Results Using conditioned media and co-culture experiments we found increased osteocyte-induced osteoclastogenesis and bone resorption in estrogen deficient conditions. This is the first study to report that administration of Scl-Ab has the ability to revert osteocyte-mediated osteoclastogenesis and resorption by decreasing RANKL/OPG ratio expression and increasing WISP1 expression in estrogen deficient osteocytes. ConclusionsThis study provides an enhanced understanding of the biological changes underpinning decreases in bone resorption following Scl-Ab treatment observed in vivo by revealing that Scl-Ab can reduce pro-osteoclastogenic cell signalling between osteocytes and osteoclasts.

Scl-Ab reverts pro-osteoclastogenic signaling and resorption in estrogen deficient osteocytes

Background Neutralising antibodies to sclerostin (Scl-Ab) have shown significant potential to induce bone formation and decrease bone resorption, increase strength and substantially reduce fracture risk in animal studies and clinical trials. Mechanical loading negatively regulates sclerostin expression, and sclerostin has been shown to induce RANKL synthesis in osteocytes. We have recently discovered that osteoblasts and osteocytes alter osteoclastogenic signalling (RANKL/OPG) during estrogen-deficiency, and that osteoblast-induced osteoclastogenesis and resorption are exacerbated. However, it is not known whether estrogen deficient osteocytes exhibit exacerbate osteoclastogenesis. The aims of this study were to (1) establish whether osteocytes induce osteoclastogenesis and bone resorption during estrogen deficiency in vitro (2) investigate whether the sclerostin antibody can revert osteocyte-mediated osteoclastogenesis and resorption by attenuating RANKL/OPG production. Results Using conditioned media and co-culture experiments we found increased osteocyte-induced osteoclastogenesis and bone resorption in estrogen deficient conditions. This is the first study to report that administration of Scl-Ab decreased RANKL/OPG ratio and increased WISP1 expression in osteocytes and reduced osteoclastogenesis and bone resorption in vitro. Conclusions This study provides an enhanced understanding of the biological changes underpinning decreases in bone resorption following Scl-Ab treatment observed in vivo by revealing that Scl-Ab can reduce pro-osteoclastogenic cell signalling between osteocytes and osteoclasts.

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowledge regarding the mechanisms that underlie the progression of osteoporosis. Emerging clinical and molecular evidence suggests that inflammation exerts a significant influence on bone turnover, thereby on osteoporosis. In this regard, MSCs have proven to possess broad immunoregulatory capabilities, modulating both adaptive and innate immunity. Here, we will discuss the role that MSCs play in the etiopathology of osteoporosis and their potential use for the treatment of this disease.

Bone Mineral Loss During Pregnancy: Is Tennis Protective?

Background:Pregnancy may stress calcium economy in women through fetal calcium requirements, and increasing maternal body weight. Bone is stimulated by compression forces. Playing tennis may decrease bone resorption through intermittent mechanical loading. This study tests the thesis that maternal bone mineral changes during pregnancy in women who play tennis are less compromised compared with nontennis playing controls.Methods:This is a prospective cohort study, a pilot study of 18 healthy pregnant women: 8 tennis players and 10 controls, ages 18 to 39 years. Calcanei bone mineral density (BMD) and ultrasound (Stiffness Index (SI)) measurements, were made at 12 weeks gestation and 2 to 4 weeks postpartum. SI was also measured at 20 to 24, and 33 to 36 weeks gestation. Statistical analysis included analysis of variance and covariance.Results:Age, height, and weight at study entry were not different between tennis players and controls. At 12 weeks, BMD was higher in tennis players versus controls 0.57 ± 0.02, 0.43 ± 0.03 g/cm2, (P = .003); but not postpartum. SI Z-scores fell significantly during pregnancy in both groups, but were consistently higher in tennis players.Conclusions:Bone measures dropped overall during pregnancy, but were significantly higher in tennis players versus controls at 12 weeks and through gestation.