Coupling is the process that links bone resorption to bone formation in a temporally and spatially coordinated manner within the remodeling cycle. Several lines of evidence point to the critical roles of osteoclast-derived coupling factors in the regulation of osteoblast performance. Here, we used a fractionated secretomic approach and identified the axon-guidance molecule SLIT3 as a clastokine that stimulated osteoblast migration and proliferation by activating β-catenin. SLIT3 also inhibited bone resorption by suppressing osteoclast differentiation in an autocrine manner. Mice deficient in Slit3 or its receptor, Robo1, exhibited osteopenic phenotypes due to a decrease in bone formation and increase in bone resorption. Mice lacking Slit3 specifically in osteoclasts had low bone mass, whereas mice with either neuron-specific Slit3 deletion or osteoblast-specific Slit3 deletion had normal bone mass, thereby indicating the importance of SLIT3 as a local determinant of bone metabolism. In postmenopausal women, higher circulating SLIT3 levels were associated with increased bone mass. Notably, injection of a truncated recombinant SLIT3 markedly rescued bone loss after an ovariectomy. Thus, these results indicate that SLIT3 plays an ...Continue Reading
Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis
Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance
Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex
Switching repulsion to attraction: changing responses to slit during transition in mesoderm migration
A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA
Mouse alpha1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast
A genetic model for a central (septum transversum) congenital diaphragmatic hernia in mice lacking Slit3
The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons
Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion
Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury
Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast-osteoblast coupling
Cables links Robo-bound Abl kinase to N-cadherin-bound beta-catenin to mediate Slit-induced modulation of adhesion and transcription
Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3
Cardiotrophin-1 is an osteoclast-derived stimulus of bone formation required for normal bone remodeling
Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate.
Cdc42 regulates bone modeling and remodeling in mice by modulating RANKL/M-CSF signaling and osteoclast polarization.
Peptide-based mediated disruption of N-cadherin-LRP5/6 interaction promotes Wnt signaling and bone formation
Afamin secreted from nonresorbing osteoclasts acts as a chemokine for preosteoblasts via the Akt-signaling pathway
Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin.
Effects of combined treatment with eldecalcitol and alendronate on bone mass, mechanical properties, and bone histomorphometry in ovariectomized rats: a comparison with alfacalcidol and alendronate
Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee
CRYAB promotes osteogenic differentiation of human bone marrow stem cells via stabilizing β-catenin and promoting the Wnt signalling
Rac1 Inhibition Via Srgap2 Restrains Inflammatory Osteoclastogenesis and Limits the Clastokine, SLIT3.
Human perivascular stem cells prevent bone graft resorption in osteoporotic contexts by inhibiting osteoclast formation.
Elevated ceramides 18:0 and 24:1 with aging are associated with hip fracture risk through increased bone resorption
Single-nucleotide polymorphism rs10036727 in the SLIT3 gene is associated with osteoporosis at the femoral neck in older Mexican postmenopausal women.
Deciphering the potential pharmaceutical mechanism of Guzhi Zengsheng Zhitongwan on rat bone and kidney based on the "kidney governing bone" theory.
Profiling the miRNA-mRNA-lncRNA interaction network in MSC osteoblast differentiation induced by (+)-cholesten-3-one
Candidate Gene and Genome-Wide Association Studies for Circulating Leptin Levels Reveal Population and Sex-Specific Associations in High Cardiovascular Risk Mediterranean Subjects
Mineral and organic matrix composition at bone forming surfaces in postmenopausal women with osteoporosis treated with either teriparatide or zoledronic acid.
Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual.
The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein.
Gamabufotalin Inhibits Osteoclastgenesis and Counteracts Estrogen-Deficient Bone Loss in Mice by Suppressing RANKL-Induced NF-κB and ERK/MAPK Pathways.
Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds.
Spatiotemporal blood vessel specification at the osteogenesis and angiogenesis interface of biomimetic nanofiber-enabled bone tissue engineering.
Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor.
An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.
Cadherins and Catenins
Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.