Osteocytes and Skeletal Pathophysiology

Delgado‐Calle, Jesús; Bellido, Teresita

doi:10.1007/s40610-015-0026-y

Cited by 49 publications

(41 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The discrepancy may be a consequence of the relatively young age of the mice used in our study. It is worth noting that other studies have also found that serum levels of sclerostin do not always correlate with Sost skeletal gene expression, which may reflect distinct paracrine and endocrine functions of sclerostin . After treatment, there is an increase in both the gene expression and circulating levels of sclerostin, demonstrating positive feedback in response to the antibody.…”

Section: Discussionmentioning

confidence: 81%

See 1 more Smart Citation

Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice

Carpenter

Ross

2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

X‐linked hypophosphatemia (XLH), caused by a loss‐of‐function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX), is the most common form of vitamin D‐resistant rickets. Loss of functional PHEX results in elevated fibroblast growth factor 23 (FGF23) levels, impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily in osteocytes, suppresses bone formation by antagonizing Wnt signaling and is reported to be elevated in XLH patients. This study used the Hyp mouse model to investigate sclerostin's role in the pathophysiology of XLH by evaluating the use of a monoclonal antibody to sclerostin in a mouse model of XLH, the Hyp mouse. Male and female wild‐type and Hyp littermates were injected with 25 mg/kg of vehicle or sclerostin antibody (Scl‐Ab) twice weekly, beginning at 4 weeks of age and euthanized at 8 weeks of age. Scl‐Ab treatment increased serum phosphate levels and suppressed circulating levels of intact FGF23 in treated wild‐type and Hyp mice of both sexes. Cortical area, trabecular bone volume fraction (BV/TV), metaphyseal apparent density, and the peak load increased with Scl‐Ab treatment in both sexes. This short‐term treatment study suggests that Scl‐Ab treatment can effectively improve some of the pathologies associated with XLH, including normalization of phosphate, and that sclerostin may play a role in regulating FGF23 and phosphate metabolism in XLH. © 2019 American Society for Bone and Mineral Research.

show abstract

Section: Discussionmentioning

confidence: 81%

“…Limitations of this study include the use of relatively young, growing animals, where sclerostin levels are expected to be lowest . Despite the low circulating sclerostin levels, Scl‐Ab treatment improved several XLH‐related pathologies in young Hyp mice.…”

Section: Discussionmentioning

confidence: 98%

Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice

Carpenter

Ross

2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…Although initially described as inactive quiescent cells buried in the mineralized tissue, osteocytes are essential for the accomplishment of the functions of the skeleton. Osteocytes coordinate bone acquisition during growth, control the maintenance of a healthy skeleton suit for locomotion, and provide protection of essential organs . Osteocytes orchestrate the work of osteoblasts that form bone and osteoclasts that resorb it by producing and secreting factors in response to environmental cues, thus adapting the skeleton to mechanical needs and hormonal changes.…”

Section: Osteocytes: Challenges and Opportunities To Study Their Rolementioning

confidence: 99%

“…A small proportion (<20%) of osteoblasts on bone surfaces become surrounded by the matrix proteins that they produce, and differentiate into osteocytes . Osteoblast–osteocyte differentiation is characterized by alterations in gene expression and is accompanied by morphological and functional cellular changes . During osteocytogenesis, the cuboidal shape of the highly secretory osteoblasts progressively changes to a star‐like morphology that characterizes the osteocytes.…”

Section: Osteocytes: Challenges and Opportunities To Study Their Rolementioning

confidence: 99%

Ex Vivo Organ Cultures as Models to Study Bone Biology

Bellido

Delgado‐Calle

2020

JBMR Plus

Self Cite

View full text Add to dashboard Cite

The integrity of the skeleton is maintained by the coordinated and balanced activities of the bone cells. Osteoclasts resorb bone, osteoblasts form bone, and osteocytes orchestrate the activities of osteoclasts and osteoblasts. A variety of in vitro approaches has been used in an attempt to reproduce the complex in vivo interactions among bone cells under physiological as well as pathological conditions and to test new therapies. Most cell culture systems lack the proper extracellular matrix, cellular diversity, and native spatial distribution of the components of the bone microenvironment. In contrast, ex vivo cultures of fragments of intact bone preserve key cell–cell and cell–matrix interactions and allow the study of bone cells in their natural 3D environment. Further, bone organ cultures predict the in vivo responses to genetic and pharmacologic interventions saving precious time and resources. Moreover, organ cultures using human bone reproduce human conditions and are a useful tool to test patient responses to therapeutic agents. Thus, these ex vivo approaches provide a platform to perform research in bone physiology and pathophysiology. In this review, we describe protocols optimized in our laboratories to establish ex vivo bone organ cultures and provide technical hints and suggestions. In addition, we present examples on how this technical approach can be employed to study osteocyte biology, drug responses in bone, cancer‐induced bone disease, and cross‐talk between bone and other organs © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

show abstract

“…These actions are controlled by osteocytes, differentiated osteoblasts embedded in the bone matrix [7]. Cell-to-cell communication via gap junctions among these cells was first appreciated in morphological studies using electron microscopy [8].…”

Section: Connexins and Pannexins In Bonementioning

confidence: 99%

Connexins and Pannexins in Bone and Skeletal Muscle

Plotkin

Davis

Cisterna

et al. 2017

Curr Osteoporos Rep

View full text Add to dashboard Cite

Purpose of review To discuss the current knowledge on the role of connexins and pannexins in the musculoskeletal system. Recent findings Connexins and pannexins are crucial for the development and maintenance of both bone and skeletal muscle. In bone, the existence of connexin and more recently pannexin channels in osteoblasts, osteoclasts, and osteocytes has been described, and shown to be essential for normal skeletal development and bone adaptation. In skeletal muscles, connexins and pannexins play important roles during development and regeneration through coordinated regulation of metabolic functions via cell-to-cell communication. Further, under pathological conditions, altered expression of these proteins can promote muscle atrophy and degeneration by stimulating inflammasome activity. Summary In the current review, we highlight the important roles of connexins and pannexins in the development, maintenance, and regeneration of musculoskeletal tissues, with emphasis on the mechanisms by which these molecules mediate chemical (e.g., ATP and PGE2) and physical (e.g. mechanical stimulation) stimuli that target the musculoskeletal system and their involvement in the pathophysiological changes in both genetic and acquired diseases.

show abstract

Osteocytes and Skeletal Pathophysiology

Cited by 49 publications

References 103 publications

Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice

Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice

Ex Vivo Organ Cultures as Models to Study Bone Biology

Connexins and Pannexins in Bone and Skeletal Muscle

Contact Info

Product

Resources

About