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Open AccessJournal ArticleDOI

Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation

TLDR
It is shown that osteocytes can also remove bone matrix by reversibly remodeling their perilacunar/canalicular matrix during the reproductive cycle through molecular mechanisms similar to those utilized by osteoclasts.
Abstract
Osteoclasts are thought to be solely responsible for the removal of bone matrix. However, we show here that osteocytes can also remove bone matrix by reversibly remodeling their perilacunar/canalicular matrix during the reproductive cycle. In contrast, no osteocytic remodeling was observed with experimental unloading despite similar degrees of bone loss. Gene array analysis of osteocytes from lactating animals revealed an elevation of genes known to be utilized by osteoclasts to remove bone, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, that returned to virgin levels upon weaning. Infusion of parathyroid hormone-related peptide (PTHrP), known to be elevated during lactation, induced TRAP activity and cathepsin K expression in osteocytes concurrent with osteocytic remodeling. Conversely, animals lacking the parathyroid hormone type 1 receptor (PTHR1) in osteocytes failed to express TRAP or cathepsin K or to remodel their osteocyte perilacunar matrix during lactation. These studies show that osteocytes remove mineralized matrix through molecular mechanisms similar to those utilized by osteoclasts.

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Citations
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Journal ArticleDOI

The Osteocyte: An Endocrine Cell … and More

TL;DR: The osteocytes encased within mineralized bone matrix are actually multifunctional cells with many key regulatory roles in bone and mineral homeostasis and should be considered in new strategies to prevent and treat bone disease.
Journal ArticleDOI

Targeting cellular senescence prevents age-related bone loss in mice

TL;DR: A causal role for senescent cells in bone loss with aging is established, and targeting these cells has both anti-resorptive and anabolic effects on bone, which suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.
Journal ArticleDOI

Osteocytes: Master Orchestrators of Bone

TL;DR: How a highly productive combination of experimental and theoretical approaches has managed to unearth unique features of osteocytes and bring to light novel insights into the regulatory mechanisms operating in bone is discussed.
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Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

TL;DR: This review addresses the current knowledge regarding maternal adaptations in mineral and skeletal homeostasis that occur during pregnancy, lactation, and post-weaning recovery and the impacts that these adaptations have on biochemical and hormonal parameters of mineralHomeostasis.
References
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Journal ArticleDOI

The Amazing Osteocyte

TL;DR: Osteocytes compose 90% to 95% of all bone cells in adult bone and are the longest lived bone cell, up to decades within their mineralized environment.
Journal ArticleDOI

Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism

TL;DR: Mechanistic studies using Dmp1-null mice demonstrated that absence of DMP1 results in defective osteocyte maturation and increased FGF23 expression, leading to pathological changes in bone mineralization, suggesting a bone-renal axis that is central to guiding proper mineral metabolism.
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Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation

TL;DR: In vivo evidence is provided for the first time to support the concept that osteocytes secrete sclerostin after they become embedded in a mineralized matrix to limit further bone formation by osteoblasts and propose that sclerOSTin production by osteocytes may regulate the linear extent of formation and the induction or maintenance of a lining cell phenotype on bone surfaces.
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