Sclerostin antibody - Sclerostin is a secreted glycoprotein with a protein sequence similar to the bone morphogenic protein antagonist family. The protein is encoded by the SOST gene in humans. It is produced by the osteocyte and down regulates osteoblastic bone formation.
Recently, sclerostin has been implicated in the inhibition of Wnt signaling leading to attenuated bone formation and growth, acting as a stop signal to decrease bone formation by osteoblasts. Mutations in sclerostin are a result from early stop signals during protein production, leading to uninhibited Wnt signaling and bone overgrowth. The mutations in this process can lead to a range of diseases, such as type II diabetes, breast and prostate cancer.
Production of this protein is inhibited by parathyroid hormone, leading to enhanced release of the calcium from the large reservoir contained in the bones, indirectly stimulating bone resorption by osteoclasts, and various other cytokines. Production of this protein is stimulated by calcitonin, a hormone which acts to reduce blood calcium levels that acts in opposition to the parathyroid hormone.
Bone remodelling is the process by which the adult skeleton is continually renewed through the highly coordinated activity of three types of cells, which are osteoclasts, osteoblasts, and osteocytes. Disruptions in signalling among these cells and alterations in their activity have been associated with skeletal diseases such as 'van Buchem disease'.
Mutations in the sclerostin gene are associated with the autosomal-recessive disorder called sclerosteosis, in addition to other disorders characterized by bone overgrowth. Sclerosteosis is a rare disorder characterized by bone over growth primarily in the skull, mandible and long, tubular bones. Individual affected with this homozygous disorder have no detectable levels of circulating sclerostin. However, heterozygous individuals for the mutations express the normal phenotype and normal lifespan, with dense bones and a low risk for fracture. This observation has led to the development of a novel strategy to emulate the heterozygous mutational state as an effective treatment for bone loss disorders such as osteoporosis.
Sclerostin is the subject of key research into both bone overgrowth and bone loss. As Sclerostin antibody could potentially increase bone formation significantly without effecting bone resorption and enhance bone strength. Thus, sclerostin antibody can potentially alleviate osteoporosis disease, this occurs when bones become fragile and more likely to fracture.
This has been established in numerous clinical trials in rats, monkeys, and in humans. It has been recognized that the absence of the sclerostin protein leads to bone overgrowth. Whereas an excess amount of sclerostin leads to bone loss and reduced bone strength. This was proved in various trials, for instance the trial on a six month old female rats was a success. Once the sclerostin antibody was administered, it quickly created an increase in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. For the human clinical trials, it was a success in healthy men and postmenopausal women (72 targets), as the antibody was tolerated well, which was the palpable primary goal. Additionally, the targets had augmented bone density for hip fractures and in their spine. Methods to increase bone in humans have long been sought. The bone formation axis controlled by sclerostin may provide an important new strategy to accomplish this. Thus, Sclerostin asserts itself as a prime therapeutic target to address bone disorders. The modification of its activity or expression offers an exciting possibility for the development of new drugs for the treatment of disorders associated with bone loss.
This antibody is for research use only and can be used on the following applications, WB (western blot), IHC-P(immunohistochemistry), and P-ELISA.
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