scholarly journals Osteoblastic Wnt1 regulates periosteal bone formation in adult mice

Bone ◽  
2021 ◽  
Vol 143 ◽  
pp. 115754
Author(s):  
Fan Wang ◽  
Petri Rummukainen ◽  
Terhi J. Heino ◽  
Riku Kiviranta
Keyword(s):  
Bone Formation ◽  
Periosteal Bone Formation ◽  
Adult Mice

scholarly journals Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Scott A. Scarneo ◽  
Liesl S. Eibschutz ◽  
Phillip J. Bendele ◽  
Kelly W. Yang ◽  
Juliane Totzke ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Bone Formation ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Cartilage Damage ◽  
Cytokine Signaling ◽  
Periosteal Bone Formation ◽  
Bone Width

Abstract Objectives To examine the ability of takinib, a selective transforming growth factor beta-activated kinase 1 (TAK1) inhibitor, to reduce the severity of murine type II collagen-induced arthritis (CIA), and to affect function of synovial cells. Methods Following the induction of CIA, mice were treated daily with takinib (50 mg/kg) and clinical scores assessed. Thirty-six days post-CIA induction, histology was performed on various joints of treated and vehicle-treated animals. Inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation were quantified. Furthermore, pharmacokinetics of takinib were evaluated by LC-MS in various tissues. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells were cultured with 10 μM takinib and cytokine secretion analyzed by cytokine/chemokine proteome array. Cytotoxicity of takinib for RA-FLS was measured with 24 to 48 h cultures in the presence or absence of tumor necrosis factor (TNF). Results Here, we show takinib’s ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling. Conclusion Our findings support the hypothesis that TAK1 targeted therapy represents a novel therapeutic axis to treat RA and other inflammatory diseases.

Dissociation of bone resorption and bone formation in adult mice transplanted with OC/OC hematopoietic stem cells

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S139
Author(s):  
C. Flores ◽  
C.S. Thudium ◽  
G. Langenbach ◽  
M. Brüel ◽  
N.A. Sims ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Resorption ◽  
Bone Formation ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
Adult Mice

scholarly journals Intermittent PTH stimulates periosteal bone formation by actions on post-mitotic preosteoblasts

Bone ◽  
2009 ◽  
Vol 44 (2) ◽  
pp. 275-286 ◽  
Author(s):  
Robert L. Jilka ◽  
Charles A. O'Brien ◽  
A. Afshan Ali ◽  
Paula K. Roberson ◽  
Robert S. Weinstein ◽  
...  
Keyword(s):  
Bone Formation ◽  
Periosteal Bone Formation ◽  
Intermittent Pth

Odanacatib treatment increases femoral periosteal bone formation in the estrogen-deficient adult rhesus monkeys

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S35-S36
Author(s):  
B.L. Pennypacker ◽  
T. Cusick ◽  
G.A. Wesolowski ◽  
D. Kimmel ◽  
L.T. Duong⁎
Keyword(s):  
Bone Formation ◽  
Rhesus Monkeys ◽  
Periosteal Bone Formation

Effect of spaceflight on periosteal bone formation in rats

1983 ◽  
Vol 244 (3) ◽  
pp. R305-R309 ◽  
Author(s):  
T. J. Wronski ◽  
E. R. Morey
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Wistar Rats ◽  
Periosteal Bone Formation ◽  
Mechanical Unloading ◽  
Before And After ◽  
Male Wistar Rats ◽  
Endocrine Factors ◽  
Nonsignificant Decrease

Male Wistar rats were placed in orbit for 18.5 days aboard the Soviet COSMOS 1129 biological satellite. Tetracycline was administered before and after spaceflight to label areas of bone formation. An inhibition of periosteal bone formation occurred during spaceflight in the tibial and humeral diaphyses, but this defect was corrected during the postflight period. The increased extent of arrest lines at these skeletal sites suggested that periosteal bone formation may have even ceased during spaceflight. The rib exhibited a small but nonsignificant decrease in periosteal bone formation. Endosteal bone resorption was not affected markedly by spaceflight conditions. The observed inhibition of periosteal bone formation may be a result of mechanical unloading, but endocrine factors cannot be ruled out.

scholarly journals Gut microbiota induce IGF-1 and promote bone formation and growth

2016 ◽  
Vol 113 (47) ◽  
pp. E7554-E7563 ◽  
Author(s):  
Jing Yan ◽  
Jeremy W. Herzog ◽  
Kelly Tsang ◽  
Caitlin A. Brennan ◽  
Maureen A. Bower ◽  
...  
Keyword(s):  
Bone Formation ◽  
Gut Microbiota ◽  
Bone Mass ◽  
Bone Growth ◽  
Serum Levels ◽  
Short Chain Fatty Acids ◽  
Skeletal Growth ◽  
Microbial Colonization ◽  
Adult Mice ◽  
Specific Pathogen

Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.

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