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Current Osteoporosis Reports Feb 2021Skeletal adaptation to mechanical loading plays a critical role in bone growth and the maintenance of bone homeostasis. Osteocytes are postulated to serve as a hub... (Review)
Review
PURPOSE OF REVIEW
Skeletal adaptation to mechanical loading plays a critical role in bone growth and the maintenance of bone homeostasis. Osteocytes are postulated to serve as a hub orchestrating bone remodeling. The recent findings on the molecular mechanisms by which osteocytes sense mechanical loads and the downstream bone-forming factors are reviewed.
RECENT FINDINGS
Calcium channels have been implicated in mechanotransduction in bone cells for a long time. Efforts have been made to identify a specific calcium channel mediating the skeletal response to mechanical loads. Recent studies have revealed that Piezo1, a mechanosensitive ion channel, is critical for normal bone growth and is essential for the skeletal response to mechanical loading. Identification of mechanosensors and their downstream effectors in mechanosensing bone cells is essential for new strategies to modulate regenerative responses and develop therapies to treat the bone loss related to disuse or advanced age.
Topics: Animals; Bone Remodeling; Calcium Channels; Humans; Ion Channels; Mechanotransduction, Cellular; Osteocytes
PubMed: 33420631
DOI: 10.1007/s11914-020-00650-y -
Frontiers in Endocrinology 2023Osteocyte, a cell type living within the mineralized bone matrix and connected to each other by means of numerous dendrites, appears to play a major role in body... (Review)
Review
Osteocyte, a cell type living within the mineralized bone matrix and connected to each other by means of numerous dendrites, appears to play a major role in body homeostasis. Benefiting from the maturation of osteocyte extraction and culture technique, many cross-sectional studies have been conducted as a subject of intense research in recent years, illustrating the osteocyte-organ/tissue communication not only mechanically but also biochemically. The present review comprehensively evaluates the new research work on the possible crosstalk between osteocyte and closely situated or remote vital organs/tissues. We aim to bring together recent key advances and discuss the mutual effect of osteocyte and brain, kidney, vascular calcification, muscle, liver, adipose tissue, and tumor metastasis and elucidate the therapeutic potential of osteocyte.
Topics: Humans; Osteocytes; Animals; Cell Communication; Brain; Adipose Tissue; Kidney
PubMed: 38685911
DOI: 10.3389/fendo.2023.1308408 -
Current Osteoporosis Reports Dec 2017Multiple dietary components have the potential to positively affect bone mineral density in early life and reduce loss of bone mass with aging. In addition, regular... (Review)
Review
PURPOSE OF REVIEW
Multiple dietary components have the potential to positively affect bone mineral density in early life and reduce loss of bone mass with aging. In addition, regular weight-bearing physical activity has a strong positive effect on bone through activation of osteocyte signaling. We will explore possible synergistic effects of dietary components and mechanical stimuli for bone health by identifying dietary components that have the potential to alter the response of osteocytes to mechanical loading.
RECENT FINDINGS
Several (sub)cellular aspects of osteocytes determine their signaling towards osteoblasts and osteoclasts in response to mechanical stimuli, such as the osteocyte cytoskeleton, estrogen receptor α, the vitamin D receptor, and the architecture of the lacunocanalicular system. Potential modulators of these features include 1,25-dihydroxy vitamin D, several forms of vitamin K, and the phytoestrogen genistein. Multiple dietary components potentially affect osteocyte function and therefore may have a synergistic effect on bone health when combined with a regime of physical activity.
Topics: Bone Density; Bone and Bones; Calcitriol; Diet; Estrogen Receptor alpha; Exercise; Genistein; Humans; Mechanotransduction, Cellular; Osteoblasts; Osteoclasts; Osteocytes; Receptors, Calcitriol; Resistance Training; Signal Transduction; Vitamin K; Weight-Bearing
PubMed: 29098573
DOI: 10.1007/s11914-017-0406-8 -
Frontiers in Endocrinology 2020Osteocytes, which represent up to 95% of adult skeletal cells, are deeply embedded in bone. These cells exhibit important interactive abilities with other bone cells... (Review)
Review
Osteocytes, which represent up to 95% of adult skeletal cells, are deeply embedded in bone. These cells exhibit important interactive abilities with other bone cells such as osteoblasts and osteoclasts to control skeletal formation and resorption. Beyond this local role, osteocytes can also influence the function of distant organs due to the presence of their sophisticated lacunocanalicular system, which connects osteocyte dendrites directly to the vasculature. Through these networks, osteocytes sense changes in circulating metabolites and respond by producing endocrine factors to control homeostasis. One critical function of osteocytes is to respond to increased blood phosphate and 1,25(OH) vitamin D (1,25D) by producing fibroblast growth factor-23 (FGF23). FGF23 acts on the kidneys through partner fibroblast growth factor receptors (FGFRs) and the co-receptor Klotho to promote phosphaturia a downregulation of phosphate transporters, as well as the control of vitamin D metabolizing enzymes to reduce blood 1,25D. In the first part of this review, we will explore the signals involved in the positive and negative regulation of FGF23 in osteocytes. In the second portion, we will bridge bone responses with the review of current knowledge on FGF23 endocrine functions in the kidneys.
Topics: Animals; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Humans; Kidney; Kidney Diseases; Klotho Proteins; Osteocytes; Signal Transduction
PubMed: 32982979
DOI: 10.3389/fendo.2020.00592 -
Endocrinology and Metabolism Clinics of... Mar 2017When normal physiologic functions go awry, disorders and disease occur. This is universal; even for the osteocyte, a cell embedded within the mineralized matrix of bone.... (Review)
Review
When normal physiologic functions go awry, disorders and disease occur. This is universal; even for the osteocyte, a cell embedded within the mineralized matrix of bone. It was once thought that this cell was simply a placeholder in bone. Within the last decade, the number of studies of osteocytes has increased dramatically, leading to the discovery of novel functions of these cells. With the discovery of novel physiologic functions came the discoveries of how these cells can also be responsible for not only bone diseases and disorders, but also those of the kidney, heart, and potentially muscle.
Topics: Bone Diseases; Bone and Bones; Fibroblast Growth Factor-23; Heart Diseases; Humans; Kidney Diseases; Muscular Diseases; Osteocytes
PubMed: 28131126
DOI: 10.1016/j.ecl.2016.09.003 -
Journal of Musculoskeletal & Neuronal... Sep 2018Osteocytes, the most abundant bone cell in the adult skeleton, can function as mechanosensors directing osteoblast and osteoclast function in order to maintain optimal... (Review)
Review
Osteocytes, the most abundant bone cell in the adult skeleton, can function as mechanosensors directing osteoblast and osteoclast function in order to maintain optimal load bearing bone in addition to functioning as endocrine cells regulating phosphate metabolism. A controversial function, previously overlooked or denied, has been osteocytes as regulators of calcium metabolism. Early histologists upon observing enlarged osteocyte lacunae in bone sections proposed that mature osteocytes could remove their perilacunar matrix, a term called "osteocytic osteolysis". New insights into this process have occurred during the last decade using novel technology thereby providing a means to identify molecular mechanisms responsible for osteocytic osteolysis. As release of calcium from a mineralized matrix requires a more acidic pH and specialized enzymes, it was proposed that osteocytes may utilize similar molecular mechanisms as osteoclasts to remove mineral. The idea that a cell descended from mesenchymal progenitors (the osteocyte) could function similarly to a cell descended from hematopoietic progenitors (the osteoclast) was challenged as being improbable. Here we review the molecular mechanisms behind this osteocyte function, the role of osteocytic osteolysis in health and disease, and the capacity of the osteocyte to reverse the osteolytic process by replacing the removed matrix, a revived osteoblast function.
Topics: Animals; Bone Remodeling; Calcium; Humans; Osteocytes; Osteolysis; Parathyroid Hormone
PubMed: 30179206
DOI: No ID Found -
Journal of Dental Research Aug 2018In lamellar bone, a network of highly oriented interconnected osteocytes is organized in concentric layers. Through their cellular processes contained within canaliculi,... (Review)
Review
In lamellar bone, a network of highly oriented interconnected osteocytes is organized in concentric layers. Through their cellular processes contained within canaliculi, osteocytes are highly mechanosensitive and locally modulate bone remodeling. We review the recent developments demonstrating the significance of the osteocyte lacuno-canalicular network in bone maintenance around implant biomaterials. Drilling during implant site preparation triggers osteocyte apoptosis, the magnitude of which correlates with drilling speed and heat generation, resulting in extensive remodeling and delayed healing. In peri-implant bone, osteocytes physically communicate with implant surfaces via canaliculi and are responsive to mechanical loading, leading to changes in osteocyte numbers and morphology. Certain implant design features allow peri-implant osteocytes to retain a less aged phenotype, despite highly advanced extracellular matrix maturation. Physicochemical properties of anodically oxidized surfaces stimulate bone formation and remodeling by regulating the expression of RANKL (receptor activator of nuclear factor-κB ligand), RANK, and OPG (osteoprotegerin) from implant-adherent cells. Modulation of certain osteocyte-related molecular signaling mechanisms (e.g., sclerostin blockade) may enhance the biomechanical anchorage of implants. Evaluation of the peri-implant osteocyte lacuno-canalicular network should therefore be a necessary component in future investigations of osseointegration to more completely characterize the biological response to materials for load-bearing applications in dentistry and orthopedics.
Topics: Animals; Biocompatible Materials; Bone Remodeling; Bone-Implant Interface; Dental Implants; Humans; Osseointegration; Osteocytes; Osteogenesis; Surface Properties
PubMed: 29863948
DOI: 10.1177/0022034518778033 -
Bone Mar 2017Sclerostin, the product of the SOST gene, is a secreted inhibitor of Wnt signaling that is produced by osteocytes to regulate bone formation. While it is often... (Review)
Review
Sclerostin, the product of the SOST gene, is a secreted inhibitor of Wnt signaling that is produced by osteocytes to regulate bone formation. While it is often considered an osteocyte-specific protein, SOST expression has been reported in numerous other cell types, including hypertrophic chondrocytes and cementocytes. Of interest, SOST/sclerostin expression is altered in certain pathogenic conditions, including osteoarthritis and rheumatic joint disease, and it is unclear whether sclerostin plays a protective role or whether sclerostin may mediate disease pathogenesis. Therefore, as anti-sclerostin antibodies are being developed for the treatment of osteoporosis, it is important to understand the functions of sclerostin beyond the regulation of bone formation.
Topics: Animals; Bone Morphogenetic Proteins; Disease; Humans; Organ Specificity; Osteocytes
PubMed: 27888056
DOI: 10.1016/j.bone.2016.11.024 -
Current Osteoporosis Reports Feb 2018Solute transport in the lacunar-canalicular system (LCS) plays important roles in osteocyte metabolism and cell-cell signaling. This review will summarize recent studies... (Review)
Review
PURPOSE OF REVIEW
Solute transport in the lacunar-canalicular system (LCS) plays important roles in osteocyte metabolism and cell-cell signaling. This review will summarize recent studies that establish pericellular matrix (PCM), discovered inside the LCS, as a crucial regulator of solute transport in bone.
RECENT FINDINGS
Utilizing confocal imaging and mathematical modeling, recent studies successfully quantified molecular diffusion and convection in the LCS as well as the size-dependent sieving effects of the PCM, leading to the quantification of the effective PCM fiber spacing (10 to 17 nm) in murine adult bones. Perlecan/HSPG2, a large linear proteoglycan, was identified to be an essential PCM component. The PCM-filled LCS is bone's chromatographic column, where fluid/solute transport to and from the osteocytes is regulated. The chemical composition, deposition rate, and turnover rate of the osteocyte PCM should be further defined to better understand osteocyte physiology and bone metabolism.
Topics: Animals; Biological Transport; Bone and Bones; Female; Male; Osteocytes
PubMed: 29349685
DOI: 10.1007/s11914-018-0414-3 -
Journal of Dental Research Jul 2016Cementum is a mineralized tissue covering the tooth root that functions in tooth attachment and posteruptive adjustment of tooth position. During formation of the... (Review)
Review
Cementum is a mineralized tissue covering the tooth root that functions in tooth attachment and posteruptive adjustment of tooth position. During formation of the apically located cellular cementum, some cementoblasts become embedded in the cementoid matrix and become cementocytes. As apparently terminally differentiated cells embedded in a mineralized extracellular matrix, cementocytes are part of a select group of specialized cells, also including osteocytes, hypertrophic chondrocytes, and odontoblasts. The differentiation and potential function(s) of cementocytes are virtually unknown, and the question may be posed whether the cementocyte is a dynamic actor in cementum in comparable fashion with the osteocyte in the skeleton, responding to changing tooth functions and endocrine signals and actively directing local cementum metabolism. This review summarizes the literature with regard to cementocytes, comparing them to their closest "cousins," the osteocytes, where insights gained from osteocyte studies serve to inform the critical examination of cementocytes. The review identifies important unanswered questions about these cells regarding their origins, differentiation, morphology and lacuno-canalicular system, selective markers, and potential functions.
Topics: Animals; Dental Cementum; Humans; Microscopy, Electron, Scanning; Osteocytes; Tooth Root
PubMed: 27029548
DOI: 10.1177/0022034516641898