Synonyms for sclerostin or Related words with sclerostin

sost              myostatin              prlr              trii              klotho              tslp              notum              netrin              rgmb              hvegf              rankl              norrin              neogenin              gpvi              mdmx              actriib              prongf              srage              tshr              lactadherin              crig              igfbp              rgma              plunc              sirp              tcblr              hdmx              sortilin              fzd              ngr              tgfrii              cypin              dkk              opticin              plexin              ctgf              tfpi              tigit              pilr              baff              periostin              crbn              pcdgf              sorla              mesothelin              tweakr              opn              galectin              actriia              chemerin             

Examples of "sclerostin"
Osteocytes synthesize sclerostin, a secreted protein that inhibits bone formation by binding to LRP5/LRP6 coreceptors and blunting Wnt signaling. Sclerostin, the product of the SOST gene, is the first mediator of communication between osteocytes, bone forming osteoblasts and bone resorbing osteoclasts, critical for bone remodeling. Only osteocytes express sclerostin, which acts in a paracrine fashion to inhibit bone formation. Sclerostin is inhibited by parathyroid hormone (PTH) and mechanical loading.
Sclerostin is a protein that in humans is encoded by the "SOST" gene.
Sclerostin, the product of the SOST gene, located on chromosome 17q12–q21 in humans, was originally believed to be a non-classical bone morphogenetic protein (BMP) antagonist. More recently sclerostin has been identified as binding to LRP5/6 receptors and inhibiting the Wnt signaling pathway. The inhibition of the Wnt pathway leads to decreased bone formation. Although the underlying mechanisms are unclear, it is believed that the antagonism of BMP-induced bone formation by sclerostin is mediated by Wnt signaling, but not BMP signaling pathways. Sclerostin is expressed in osteocytes and some chondrocytes and it inhibits bone formation by osteoblasts.
Sclerostin domain-containing protein 1 is a protein that in humans is encoded by the "SOSTDC1" gene.
Sclerostin, one of the inhibitors of LRP6, is a promising osteocyte-specific Wnt antagonist in osteoporosis clinical trials.
Romosozumab (AMG 785) is a humanized monoclonal antibody that targets sclerostin for the treatment of osteoporosis.
Sclerostin is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists. Sclerostin is produced by the osteocyte and has anti-anabolic effects on bone formation.
Sclerostin antagonizes the activity of BMP (bone morphogenetic protein), a cytokine that induces bone and cartilage formation.
Sclerostin production by osteocytes is inhibited by parathyroid hormone, mechanical loading and cytokines including prostaglandin E2, oncostatin M, cardiotrophin-1 and leukemia inhibitory factor. Sclerostin production is increased by calcitonin. Thus, osteoblast activity is self regulated by a negative feedback system.
The sclerostin protein, with a length of 213 residues, has a dssp secondary structure that is 28% beta sheet (6 strands; 32 residues).
LRP6 is regulated by extracellular proteins in the Dickkopf (Dkk) family (like DKK1), sclerostin, R-spondins and members of the cysteine-knot-type protein family.
Mutations in BMPs and their inhibitors (such as sclerostin) are associated with a number of human disorders which affect the skeleton.
Osteocyte specific proteins such as sclerostin have been shown to function in mineral metabolism, as well as other molecules such as PHEX, DMP-1, MEPE, and FGF-23, which are highly expressed by osteocytes and regulate phosphate and biomineralization.
The Amgen drug is expected to be on the market in 2017 and is predicted to be the gold standard in osteoporosis treatment by 2021. In addition, OsteoGeneX is developing small molecule inhibitors of sclerostin.
Feedback from physical activity maintains bone mass, while feedback from osteocytes limits the size of the bone-forming unit. An important additional mechanism is secretion by osteocytes, buried in the matrix, of sclerostin, a protein that inhibits a pathway that maintains osteoblast activity. Thus, when the osteon reaches a limiting size, it inactivates bone synthesis.
This gene is a member of the sclerostin family and encodes an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. This protein functions as a bone morphogenetic protein (BMP) antagonist. Specifically, it directly associates with BMPs, prohibiting them from binding their receptors, thereby regulating BMP signaling during cellular proliferation, differentiation, and programmed cell death.
An antibody for sclerostin is being developed because of the protein’s specificity to bone. Its use has increased bone growth in preclinical trials in osteoporotic rats and monkeys. In a Phase I study, a single dose of anti-sclerostin antibody from Amgen (Romosozumab) increased bone density in the hip and spine in healthy men and postmenopausal women and the drug was well tolerated. In a Phase II trial, one year of the antibody treatment in osteoporotic women increased bone density more than bisphosphonate and teriparatide treatment; it had mild injection side effects. A Phase II trial of a monoclonal human antibody to sclerostin from Eli Lilly had positive effects on post-menopausal women. Monthly treatments of the antibody for one year increased the bone mineral density of the spine and hip by 18 percent and 6 percent, respectively, compared to the placebo group. In a Phase III trial, one year of Romosozumab treatment in post-menopausal women reduced the risk of vertebral fractures compared to the placebo group. It also increased the bone mineral density in the lumbar spine (13.3% versus 0.0%), femoral neck (5.2% versus -0.7%) and total hip (6.8% versus 0.0%) compared to the placebo group. Adverse events were balanced between the groups.
Mutations in the gene that encodes the sclerostin protein are associated with disorders associated with high bone mass, sclerosteosis and van Buchem disease. Sclerosteosis is an autosomal recessive disorder characterized by bone overgrowth. It was first described in 1958 but given the current name in 1967. Excessive bone formation is most prominent in the skull, mandible and tubular bones. It can cause facial distortion and syndactyly. Increased intracranial pressure can cause sudden death in patients. It is a rare disorder that is most prominent in the Afrikaner population in South Africa (40 patients), but there have also been cases of American and Brazilian families.
The Wnt signaling pathway was first linked to bone development when a loss-of-function mutation in LRP5 was found to cause osteoporosis-pseudoglioma syndrome. Shortly thereafter, two studies reported that gain-of-function mutations in LRP5 caused high bone mass. Many bone density related diseases are caused by mutations in the LRP5 gene. There is controversy whether bone grows through Lrp5 through bone or the intestine. The majority of the current data supports the concept that bone mass is controlled by LRP5 through the osteocytes. Mice with the same Lrp5 gain-of-function mutations as also have high bone mass. The high bone mass is maintained when the mutation only occurs in limbs or in cells of the osteoblastic lineage. Bone mechanotransduction occurs through Lrp5 and is suppressed if Lrp5 is removed in only osteocytes. There are promising osteoporosis clinical trials targeting sclerostin, an osteocyte-specific protein which inhibits Wnt signaling by binding to Lrp5. An alternative model that has been verified in mice and in humans is that Lrp5 controls bone formation by inhibiting expression of TPH1, the rate-limiting biosynthetic enzyme for serotonin, a molecule that regulates bone formation, in enterochromaffin cells of the duodenum and that excess plasma serotonin leads to inhibition in bone. Another study found that a different Tph1-inhibitor decreased serotonin levels in the blood and intestine, but did not affect bone mass or markers of bone formation.