TNF ‐polarized macrophages produce insulin like 6 peptide to stimulate bone formation in rheumatoid arthritis in mice

2021 ◽  
Author(s):  
Xiangjiao Yi ◽  
Xin Liu ◽  
H. Mark Kenney ◽  
Rong Duan ◽  
Xi Lin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Formation ◽  
Stimulate Bone Formation

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.

scholarly journals Anabolic Therapies in Osteoporosis and Bone Regeneration

2018 ◽  
Vol 20 (1) ◽  
pp. 83 ◽  
Author(s):  
Gabriele Russow ◽  
Denise Jahn ◽  
Jessika Appelt ◽  
Sven Märdian ◽  
Serafeim Tsitsilonis ◽  
...  
Keyword(s):  
Bone Formation ◽  
Fracture Healing ◽  
Bone Regeneration ◽  
Treatment Options ◽  
Therapeutic Approaches ◽  
Delayed Fracture ◽  
Stimulate Bone Formation ◽  
Intrinsic Factors ◽  
Delayed Fracture Healing ◽  
Extrinsic And Intrinsic Factors

Osteoporosis represents the most common bone disease worldwide and results in a significantly increased fracture risk. Extrinsic and intrinsic factors implicated in the development of osteoporosis are also associated with delayed fracture healing and impaired bone regeneration. Based on a steadily increasing life expectancy in modern societies, the global implications of osteoporosis and impaired bone healing are substantial. Research in the last decades has revealed several molecular pathways that stimulate bone formation and could be targeted to treat both osteoporosis and impaired fracture healing. The identification and development of therapeutic approaches modulating bone formation, rather than bone resorption, fulfils an essential clinical need, as treatment options for reversing bone loss and promoting bone regeneration are limited. This review focuses on currently available and future approaches that may have the potential to achieve these aims.

scholarly journals Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Dulshara Sachini Amarasekara ◽  
Jiyeon Yu ◽  
Jaerang Rho
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Loss ◽  
Bone Formation ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Inflammatory Cytokine ◽  
Systemic Lupus ◽  
Cytokine Network ◽  
Inflammatory Bowel ◽  
Inflammatory Autoimmune Diseases

Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases.

Growth factors to stimulate bone formation

2009 ◽  
Vol 8 (S2) ◽  
pp. S565-S572 ◽  
Author(s):  
David J. Baylink ◽  
Richard D. Finkelman ◽  
Subburaman Mohan
Keyword(s):  
Growth Factors ◽  
Bone Formation ◽  
Stimulate Bone Formation

Phenytoin and fluoride act in concert to stimulate bone formation and to increase bone volume in adult male rats

1995 ◽  
Vol 56 (5) ◽  
pp. 390-397 ◽  
Author(s):  
T. Ohta ◽  
J. E. Wergedal ◽  
T. Matsuyama ◽  
D. J. Baylink ◽  
K. -H. Wiliam Lau
Keyword(s):  
Bone Formation ◽  
Adult Male ◽  
Bone Volume ◽  
Male Rats ◽  
Stimulate Bone Formation

5. Reduced bone formation in non-steroid treated patients with rheumatoid arthritis

Bone ◽  
1989 ◽  
Vol 10 (2) ◽  
pp. 144-145
Author(s):  
S Vedi ◽  
PI Croucher ◽  
MM O'Sullivan ◽  
JE Compston
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Formation

Tacrolimus treatment increases bone formation in patients with rheumatoid arthritis

2012 ◽  
Vol 33 (8) ◽  
pp. 2159-2163 ◽  
Author(s):  
Kwi Young Kang ◽  
Ji Hyeon Ju ◽  
Yeong Wook Song ◽  
Dae-Hyun Yoo ◽  
Ho-Youn Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Formation

scholarly journals Can anodised zirconium implants stimulate bone formation? Preliminary study in rat model

2014 ◽  
Vol 3 (1) ◽  
Author(s):  
Maria R. Katunar ◽  
Andrea Gomez Sanchez ◽  
Josefina Ballarre ◽  
Matias Baca ◽  
Carlos Vottola ◽  
...  
Keyword(s):  
Bone Formation ◽  
Rat Model ◽  
Stimulate Bone Formation ◽  
Preliminary Study
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