scholarly journals Osteoclasts and Microgravity

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 207
Author(s):  
John Kelly Smith
Keyword(s):  
Nuclear Factor Kappa B ◽  
Simulated Microgravity ◽  
Osteoclast Differentiation ◽  
Zero Gravity ◽  
Hematopoietic Stem ◽  
Receptor Activator ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Musculoskeletal Systems ◽  
Stimulating Factor

Astronauts are at risk of losing 1.0% to 1.5% of their bone mass for every month they spend in space despite their adherence to diets and exercise regimens designed to protect their musculoskeletal systems. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells and the contributions macrophage colony stimulating factor, receptor activator of the nuclear factor-kappa B ligand, and the calcineurin pathways make in osteoclast differentiation and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in space, and under conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

scholarly journals Osteoclasts and Microgravity

2020 ◽  
Author(s):  
John Smith
Keyword(s):  
Simulated Microgravity ◽  
Training Programs ◽  
Osteoclast Differentiation ◽  
High Impact ◽  
Zero Gravity ◽  
Hematopoietic Stem ◽  
Macrophage Colony Stimulating Factor ◽  
Impact Exercise ◽  
Macrophage Colony ◽  
Stimulating Factor

Astronauts are at risk of losing 1.0 to 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and dietary regimens designed to preserve their musculoskeletal system. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells, the contributions of macrophage colony stimulating factor, activator of NFkB and the calcineurin pathways make in osteoclast differentiation, and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in the microgravity of space, and in conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

scholarly journals Efficiency of Estrogen Replacement Therapy in Osteoporosis

2018 ◽  
Vol 3 (3) ◽  
pp. 134
Author(s):  
Syed Mohammad Mazhar Uddin ◽  
Aatera Haq ◽  
Haris Sheikh ◽  
Uzair Yaqoob ◽  
Bushra Zafar Sayeed
Keyword(s):  
Nuclear Factor Kappa B ◽  
Calcium Absorption ◽  
Estrogen Therapy ◽  
Nuclear Factor ◽  
Colony Stimulating Factor ◽  
Nuclear Factor Kappa ◽  
Receptor Activator ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Estrogen therapy has been taken as a settled approach for both prevention and treatment of osteoporosis, especially in post-menopausal women as well as for the treatment of symptoms associated with menopause. Recent studies suggest that nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B/osteoprotegerin system plays a signi cant role in osteoclastic activity regulation, with receptor activator of nuclear factor kappa-B ligand signaling in the presence of macrophage colony stimulating factor leading to increase in osteoclastic differentiation and functioning while osteoprotegerin neutralizing receptor activator of nuclear factor kappa-B ligand. Estrogen acts by increasing osteoprotegerin levels, and decreasing macrophage colony stimulating factor and receptor activator of nuclear factor kappa-B, thereby reducing bone resorption. Furthermore, estrogen is also known to be causing increased calcium absorption through gut and kidneys. The use of estrogen therapy in patients of osteoporosis is also considered to be highly cost effective. On the negative side, studies have shown that oral estrogen therapy can lead to complications like cholelithiasis, thrombophlebitis and pulmonary embolism, the most detrimental being endometrial cancer. But studies have shown that it can be virtually eliminated with the addition of progesterone in the cyclic combined regimen. Majority of bene cial effects occur with long term use of estrogen therapy, but the compliance by most of women appears to be poor and is usually due to lack of awareness, misconceptions, advice of physician and phobia of side effects. Additional studies should therefore be conducted to evaluate in detail the causes of non-compliance and strategies to improve compliance. The bene t of quality of life improvement with estrogen therapy should be taken into account and further evaluated via studies.

scholarly journals Osteoclast biology in bone resorption: a review

STEMedicine ◽  
2020 ◽  
Vol 1 (4) ◽  
pp. e57
Author(s):  
Chao Fu ◽  
Ruyi Shi
Keyword(s):  
Bone Resorption ◽  
Nuclear Factor Kappa B ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Factors Affecting ◽  
Multinucleated Cells ◽  
Cellular Factors ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

What we know about bone resorption has changed a lot in the last few decades. The osteoclast is the only cell to nibble and break down the bone, and in the formation and resorption of bone tissue, osteoclasts play an important role. Once the balance of bone formation and bone loss is out of control, diseases like osteopetrosis and osteoporosis occur. Bone resorption is a unique function of osteoblasts, which are multinucleated cells formed by the fusion of mononuclear progenitor cells of the monocyte/macrophage family. In the formation of osteoclasts, there are two main factors affecting this process, macrophage colony-stimulating factor (M-CSF) and ligand-activated receptor (RANKL) of nuclear factor kappa B (NF-κB). The identification of RANK-RANKL signaling and other classic signaling pathways such as Wnt and Notch, as the major signaling regulation in osteoclast differentiation, was a significant breakthrough in the field of osteoclastogenesis. In this review, we briefly describe the latest knowledge of osteoclast-induced bone resorption and cellular factors that regulate the activity of osteoclasts and cell fusion, for the purpose of understanding osteoclastogenesis and the development of drugs that enhance bone resorption to improve pathological bone diseases.

Phase I Study of Chimeric Human/Murine Anti–Ganglioside GD2Monoclonal Antibody (ch14.18) With Granulocyte-Macrophage Colony-Stimulating Factor in Children With Neuroblastoma Immediately After Hematopoietic Stem-Cell Transplantation: A Children’s Cancer Group Study

2000 ◽  
Vol 18 (24) ◽  
pp. 4077-4085 ◽  
Author(s):  
M. Fevzi Ozkaynak ◽  
Paul M. Sondel ◽  
Mark D. Krailo ◽  
Jacek Gan ◽  
Brad Javorsky ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Neuroblastoma Cells ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE: Ganglioside GD2is strongly expressed on the surface of human neuroblastoma cells. It has been shown that the chimeric human/murine anti-GD2monoclonal antibody (ch14.18) can induce lysis of neuroblastoma cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The purposes of the study were (1) to determine the maximum-tolerated dose (MTD) of ch14.18 in combination with standard dose granulocyte-macrophage colony-stimulating factor (GM-CSF) for patients with neuroblastoma who recently completed hematopoietic stem-cell transplantation (HSCT), and (2) to determine the toxicities of ch14.18 with GM-CSF in this setting.PATIENTS AND METHODS: Patients became eligible when the total absolute phagocyte count (APC) was greater than 1,000/μL after HSCT. ch14.18 was infused intravenously over 5 hours daily for 4 consecutive days. Patients received GM-CSF 250 μg/m2/d starting at least 3 days before ch14.18 and continued for 3 days after the completion of ch14.18. The ch14.18 dose levels were 20, 30, 40, and 50 mg/m2/d. In the absence of progressive disease, patients were allowed to receive up to six 4-day courses of ch14.18 therapy with GM-CSF. Nineteen patients with neuroblastoma were treated.RESULTS: A total of 79 courses were administered. No toxic deaths occurred. The main toxicities were severe neuropathic pain, fever, nausea/vomiting, urticaria, hypotension, mild to moderate capillary leak syndrome, and neurotoxicity. Three dose-limiting toxicities were observed among six patients at 50 mg/m2/d: intractable neuropathic pain, grade 3 recurrent urticaria, and grade 4 vomiting. Human antichimeric antibody developed in 28% of patients.CONCLUSION: ch14.18 can be administered with GM-CSF after HSCT in patients with neuroblastoma with manageable toxicities. The MTD is 40 mg/m2/d for 4 days when given in this schedule with GM-CSF.

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