The Response of wnt/ß-Catenin Signaling Pathway in Osteocytes Under Simulated Microgravity

Yang, Xiao; Sun, Lianwen; Liang, Meng; Wang, Xiaonan; Fan, Yubo

doi:10.1007/s12217-015-9439-8

Cited by 13 publications

(5 citation statements)

References 55 publications

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“…However, osteocytic mechanotransduction in patients with a WNT1 mutation is not yet fully understood. Microgravity, or unloading, decreases WNT3a, WNT5a, DKK1, cyclinD1, LEF-1, and CX43, but increases WNT1 and SOST expression in osteocytes ( 11 , 123 ). Microgravity dramatically reduces the number of F-actin filaments in osteocytes ( 123 ).…”

Section: Wnt1 and Pls3 Mutationmentioning

confidence: 98%

“…Microgravity, or unloading, decreases WNT3a, WNT5a, DKK1, cyclinD1, LEF-1, and CX43, but increases WNT1 and SOST expression in osteocytes ( 11 , 123 ). Microgravity dramatically reduces the number of F-actin filaments in osteocytes ( 123 ). This suggests a role for WNT1 in the formation of the osteocyte cytoskeleton and in osteocyte mechanosensitivity.…”

Section: Wnt1 and Pls3 Mutationmentioning

confidence: 98%

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The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases

2020

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Osteocytes are the most abundant (~95%) cells in bone with the longest half-life (~25 years) in humans. In the past osteocytes have been regarded as vestigial cells in bone, since they are buried inside the tough bone matrix. However, during the last 30 years it has become clear that osteocytes are as important as bone forming osteoblasts and bone resorbing osteoclasts in maintaining bone homeostasis. The osteocyte cell body and dendritic processes reside in bone in a complex lacuno-canalicular system, which allows the direct networking of osteocytes to their neighboring osteocytes, osteoblasts, osteoclasts, bone marrow, blood vessels, and nerves. Mechanosensing of osteocytes translates the applied mechanical force on bone to cellular signaling and regulation of bone adaptation. The osteocyte lacuno-canalicular system is highly efficient in transferring external mechanical force on bone to the osteocyte cell body and dendritic processes via displacement of fluid in the lacuno-canalicular space. Osteocyte mechanotransduction regulates the formation and function of the osteoblasts and osteoclasts to maintain bone homeostasis. Osteocytes produce a variety of proteins and signaling molecules such as sclerostin, cathepsin K, Wnts, DKK1, DMP1, IGF1, and RANKL/OPG to regulate osteoblast and osteoclast activity. Various genetic abnormality-associated rare bone diseases are related to disrupted osteocyte functions, including sclerosteosis, van Buchem disease, hypophosphatemic rickets, and WNT1 and plastin3 mutation-related disorders. Meticulous studies during the last 15 years on disrupted osteocyte function in rare bone diseases guided for the development of various novel therapeutic agents to treat bone diseases. Studies on genetic, molecular, and cellular mechanisms of sclerosteosis and van Buchem disease revealed a role for sclerostin in bone homeostasis, which led to the development of the sclerostin antibody to treat osteoporosis and other bone degenerative diseases. The mechanism of many other rare bone diseases and the role of the osteocyte in the development of such conditions still needs to be investigated. In this review, we mainly discuss the knowledge obtained during the last 30 years on the role of the osteocyte in rare bone diseases. We speculate about future research directions to develop novel therapeutic drugs targeting osteocyte functions to treat both common and rare bone diseases.

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Section: Wnt1 and Pls3 Mutationmentioning

confidence: 98%

Section: Wnt1 and Pls3 Mutationmentioning

confidence: 98%

The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases

2020

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“…The Wnt-signaling pathway is not only involved in osteoblastic cell differentiation and bone formation but also inhibits bone resorption by blocking the receptor activator of nuclear factor-κB-ligand (RANKL)/RANK interaction [ 1 , 22 ]. Many studies in the literature have reported that when reduced mechanical loading and microgravity occur, the production of sclerostin by osteocytes increases notably, blocking Wnt binding and thus resulting ultimately in reduced osteoblast and increased osteoclast activity [ 23 , 24 , 25 ].…”

Section: Bone Loss and Osteoporosismentioning

confidence: 99%

The Effect of Space Travel on Bone Metabolism: Considerations on Today’s Major Challenges and Advances in Pharmacology

Genah

Monici

Morbidelli

2021

IJMS

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Microgravity-induced bone loss is currently a significant and unresolved health risk for space travelers, as it raises the likelihood for irreversible changes that weaken skeletal integrity and the incremental onset of fracture injuries and renal stone formation. Another issue related to bone tissue homeostasis in microgravity is its capacity to regenerate following fractures due to weakening of the tissue and accidental events during the accomplishment of particularly dangerous tasks. Today, several pharmacological and non-pharmacological countermeasures to this problem have been proposed, including physical exercise, diet supplements and administration of antiresorptive or anabolic drugs. However, each class of pharmacological agents presents several limitations as their prolonged and repeated employment is not exempt from the onset of serious side effects, which limit their use within a well-defined range of time. In this review, we will focus on the various countermeasures currently in place or proposed to address bone loss in conditions of microgravity, analyzing in detail the advantages and disadvantages of each option from a pharmacological point of view. Finally, we take stock of the situation in the currently available literature concerning bone loss and fracture healing processes. We try to understand which are the critical points and challenges that need to be addressed to reach innovative and targeted therapies to be used both in space missions and on Earth.

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“…The elevated sclerostin secretion by osteocytes also negatively regulates oasteoblast-mediated bone formation by antagonising BMP/Wnt signalling [137][138][139] . Simulated µG has been shown to depress the Wnt signalling pathway and downregulate cell cycle related genes such as Cyclin D1 in osteocyte-like cells, which could be partially restored by the administration of antibodies against sclerostin 140 . Indeed, the ablation of sclerostin or RANKL appears to be protective over unloading-induced bone loss in HLU mice models 107,141 .…”

Section: Osteocytesmentioning

confidence: 99%

“…Disassembly of F-actin filaments and short dendritic processes at cell periphery • Increased Wnt1 and Sost expression • Reduced gene and protein level of β-catenin, with no nuclear translocation • Sclerostin antibody inhibited µG-induced down regulation of Wnt target genes and sclerostin protein expression Yang et al140 …”

mentioning

confidence: 99%

The effects of microgravity on bone structure and function

et al. 2022

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Humans are spending an increasing amount of time in space, where exposure to conditions of microgravity causes 1–2% bone loss per month in astronauts. Through data collected from astronauts, as well as animal and cellular experiments conducted in space, it is evident that microgravity induces skeletal deconditioning in weight-bearing bones. This review identifies contentions in current literature describing the effect of microgravity on non-weight-bearing bones, different bone compartments, as well as the skeletal recovery process in human and animal spaceflight data. Experiments in space are not readily available, and experimental designs are often limited due to logistical and technical reasons. This review introduces a plethora of on-ground research that elucidate the intricate process of bone loss, utilising technology that simulates microgravity. Observations from these studies are largely congruent to data obtained from spaceflight experiments, while offering more insights behind the molecular mechanisms leading to microgravity-induced bone loss. These insights are discussed herein, as well as how that knowledge has contributed to studies of current therapeutic agents. This review also points out discrepancies in existing data, highlighting knowledge gaps in our current understanding. Further dissection of the exact mechanisms of microgravity-induced bone loss will enable the development of more effective preventative and therapeutic measures to protect against bone loss, both in space and possibly on ground.

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The Response of wnt/ß-Catenin Signaling Pathway in Osteocytes Under Simulated Microgravity

Cited by 13 publications

References 55 publications

The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases

The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases

The Effect of Space Travel on Bone Metabolism: Considerations on Today’s Major Challenges and Advances in Pharmacology

The effects of microgravity on bone structure and function

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