ArticleThe Journal of biological chemistry2015
The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in Osteocytes in Vitro.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers.
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Who cites it
190 citing papers in PubMed, 287 citations in OpenAlex.
- Monthly treatment with romosozumab for 1 year increases bone mineral at the hip, but not the knee, in women with chronic spinal cord injury.JBMR plus · 2024Trial
- Denosumab for Prevention of Acute Onset Immobilization-Induced Alterations of Bone Turnover: A Randomized Controlled Trial.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Trial
- Osteoporosis and Alzheimer's Disease: The Role of Sclerostin.Current osteoporosis reports · 2026Review
- Musculoskeletal decay and bone-muscle crosstalk during physical disuse: Mechanisms and integrated countermeasures.Experimental physiology · 2026Review
- Evaluating the consequences of childhood adiposity on the human plasma proteome at four timepoints across the lifecourse.Nature communications · 2026Article
- Fibroblast growth factor receptor signaling in maturing osteoblasts controls cell-matrix interactions critical for osteocyte survival.Bone research · 2026Article
- Blocking interaction of sclerostin loop3 with osteoblastic LRP4 counteracts bone loss without increasing arterial stiffness during mechanical unloading.Journal of orthopaedic translation · 2026Article
- Regulation of cAMP levels in osteocytes by mechano-sensitive focal adhesion kinase and phosphodiesterase 8A.iScience · 2026Article
- Romosozumab does not improve volumetric bone mineral density at distal radius but is associated with early changes in bone strength: a prospective study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Genome-wide CRISPR interference screen identifies Clip2 as a novel regulator of osteocyte maturation and morphology.The Journal of biological chemistry · 2026Article
- Article
- High-resolution profiling of osteocyte transcriptomes via single-nucleus RNA sequencing.JBMR plus · 2026Article
- Fibroblast Growth Factor Receptor Signaling in Maturing Osteoblasts Controls Cell-Matrix Interactions Critical for Osteocyte Survival.bioRxiv : the preprint server for biology · 2026Article
- Bone Multicellular Unit on a Chip (BMU-Chip) Subjected to Cyclic Mechanical Loading.ACS biomaterials science & engineering · 2026Article
- Article
- Aging-Driven Inter-Organ Crosstalk in Postmenopausal Osteoporosis: From Immunometabolic Drift to Multisystem Frailty.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Osteocytic Lipocalin-2 regulates bone formation locally through iron-dependent ferroptosis and Wnt suppression.Cell death discovery · 2026Article
- Effects of Mechanical Stress on Bone and Cartilage Metabolism: How Mechanical Stress Affects Energy Metabolism in Bone and Cartilage Tissues (Our Research Overview): Mini Review.International journal of molecular sciences · 2026Review
- Effects of microgravity mechanotransduction in bone tissue and cells: systematic review on primary cilium-dependent mechanisms.NPJ microgravity · 2026Article
- The development of a collagen-nanoscale hydroxyapatite three-dimensional (3D) in vitro culture system for reproducing osteocyte differentiation and tissue mineralization.Biomaterials · 2026Article
130 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Although bone responds to its mechanical environment, the cellular and molecular mechanisms underlying the response of the skeleton to mechanical unloading are not completely understood. Osteocytes are the most abundant but least understood cells in bones and are thought to be responsible for sensing stresses and strains in bone. Sclerostin, a product of the SOST gene, is produced postnatally primarily by osteocytes and is a negative regulator of bone formation. Recent studies show that SOST is mechanically regulated at both the mRNA and protein levels. During prolonged bed rest and immobilization, circulating sclerostin increases both in humans and in animal models, and its increase is associated with a decrease in parathyroid hormone. To investigate whether SOST/sclerostin up-regulation in mechanical unloading is a cell-autonomous response or a hormonal response to decreased parathyroid hormone levels, we subjected osteocytes to an in vitro unloading environment achieved by the NASA rotating wall vessel system. To perform these studies, we generated a novel osteocytic cell line (Ocy454) that produces high levels of SOST/sclerostin at early time points and in the absence of differentiation factors. Importantly, these osteocytes recapitulated the in vivo response to mechanical unloading with increased expression of SOST (3.4 ± 1.9-fold, p < 0.001), sclerostin (4.7 ± 0.1-fold, p < 0.001), and the receptor activator of nuclear factor κΒ ligand (RANKL)/osteoprotegerin (OPG) (2.5 ± 0.7-fold, p < 0.001) ratio. These data demonstrate for the first time a cell-autonomous increase in SOST/sclerostin and RANKL/OPG ratio in the setting of unloading. Thus, targeted osteocyte therapies could hold promise as novel osteoporosis and disuse-induced bone loss treatments by directly modulating the mechanosensing cells in bone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.