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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 -
Gerontology 2015Receptor activator of nuclear factor x03BA;B (RANK) and its ligand (RANKL) have originally been described for their key roles in bone metabolism and the immune system.... (Review)
Review
Receptor activator of nuclear factor x03BA;B (RANK) and its ligand (RANKL) have originally been described for their key roles in bone metabolism and the immune system. Subsequently, it has been shown that the RANKL-RANK system is critical in the formation of mammary epithelia in lactating females and the thermoregulation of the central nervous system. RANKL and RANK are under the tight control of the female sex hormones estradiol and progesterone. A reduction of the circulating female sex hormones leading to an increase in RANKL-RANK signaling is the leading cause of osteoporosis in postmenopausal women. Denosumab, a human monoclonal anti-RANKL antibody, has been approved for the treatment of postmenopausal osteoporosis, where it is showing great promise. In addition, RANKL-RANK signaling also plays a critical role in other bone pathologies, bone metastasis or hormone-driven breast cancer. This review will highlight some of the functions of RANKL-RANK in bone turnover, the immune system and brain with a focus on the regulatory role of the female sex hormones.
Topics: Bone Remodeling; Female; Humans; Immunity; Osteoprotegerin; RANK Ligand
PubMed: 25720990
DOI: 10.1159/000371845 -
International Journal of Molecular... Jan 2020Osteoporosis is a common skeletal disorder, occurring as a result of an imbalance between bone resorption and bone formation, with bone breakdown exceeding bone...
Osteoporosis is a common skeletal disorder, occurring as a result of an imbalance between bone resorption and bone formation, with bone breakdown exceeding bone building. Bone resorption inhibitors, e.g., bisphosphonates, have been designed to treat osteoporosis, while anabolic agents such as teriparatide stimulate bone formation and correct the characteristic changes in the trabecular microarchitecture. However, all of these drugs are associated with significant side effects. It is therefore crucial that we continue to research the pathogenesis of osteoporosis and seek novel modes of therapy. This editorial summarizes and discusses the themes of the fifteen articles published in the Special Issue, Osteoporosis: From Molecular Mechanisms to Therapies 2019, as part of the global picture of the current understanding of osteoporosis.
Topics: Bone Density Conservation Agents; Bone Remodeling; Bone Resorption; Bone and Bones; Humans; Osteogenesis; Osteoporosis
PubMed: 31979046
DOI: 10.3390/ijms21030714 -
Bone Feb 2021Osteocytes can resorb as well as replace bone adjacent to the expansive lacunar-canalicular system (LCS). Suppressed LCS remodeling decreases bone fracture toughness,... (Review)
Review
Osteocytes can resorb as well as replace bone adjacent to the expansive lacunar-canalicular system (LCS). Suppressed LCS remodeling decreases bone fracture toughness, but it is unclear how altered LCS remodeling impacts bone quality. The first goal of this review is to assess how LCS remodeling impacts LCS morphology as well as the composition and mechanical properties of surrounding bone tissue. The second goal is to compare tools available for the assessment of bone quality at length-scales that are physiologically-relevant to LCS remodeling. We find that changes to LCS morphology occur in response to a variety of physiological conditions and diseases and can be classified in two general phenotypes. In the 'aging phenotype', seen in aging and in some disuse models, the LCS is truncated and osteocytes apoptosis is increased. In the 'osteocytic osteolysis' phenotype, which is adaptive in some physiological settings and possibly maladaptive in others, the LCS enlarges and osteocytes generally maintain viability. Bone composition and mechanical properties vary near the osteocyte and change with at least some conditions that alter LCS morphology. However, few studies have evaluated bone composition and mechanical properties close to the LCS and so the impacts of LCS remodeling phenotypes on bone tissue quality are still undetermined. We summarize the current understanding of how LCS remodeling impacts LCS morphology, tissue-scale bone composition and mechanical properties, and whole-bone material properties. Tools are compared for assessing tissue-scale bone properties, as well as the resolution, advantages, and limitations of these techniques.
Topics: Bone Remodeling; Bone and Bones; Humans; Osteocytes; Osteolysis
PubMed: 32987198
DOI: 10.1016/j.bone.2020.115663 -
Frontiers of Oral Biology 2016Bone remodeling is a highly coordinated process responsible for bone resorption and formation. It is initiated and modulated by a number of factors including... (Review)
Review
Bone remodeling is a highly coordinated process responsible for bone resorption and formation. It is initiated and modulated by a number of factors including inflammation, changes in hormonal levels and lack of mechanical stimulation. Bone remodeling involves the removal of mineralized bone by osteoclasts followed by the formation of bone matrix through osteoblasts that subsequently becomes mineralized. In addition to the traditional bone cells (osteoclasts, osteoblasts and osteocytes) that are necessary for bone remodeling, several immune cells such as polymorphonuclear neutrophils, B cells and T cells have also been implicated in bone remodelling. Through the receptor activator of nuclear factor-x03BA;B/receptor activator of the NF-x03BA;B ligand/osteoprotegerin system the process of bone resorption is initiated and subsequent formation is tightly coupled. Mediators such as prostaglandins, interleukins, chemokines, leukotrienes, growth factors, wnt signalling and bone morphogenetic proteins are involved in the regulation of bone remodeling. We discuss here cells and mediators involved in the cellular and molecular machanisms of bone resorption and bone formation.
Topics: Bone Remodeling; Bone Resorption; Calcification, Physiologic; Humans; Inflammation Mediators; Lymphocytes; Neutrophils; Osteoblasts; Osteoclasts; Osteogenesis
PubMed: 26599113
DOI: 10.1159/000351895 -
Osteoporosis International : a Journal... Dec 2019Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity... (Review)
Review
Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity through binding to specific progesterone receptors. New estrogen-free contraceptive and its possible implication on bone turnover are discussed in this review. Insufficient bone acquisition during development and/or accelerated bone loss after attainment of peak bone mass (PBM) are 2 processes that may predispose to fragility fractures in later life. The relative importance of bone acquisition during growth versus bone loss during adulthood for fracture risk has been explored by examining the variability of areal bone mineral density (BMD) (aBMD) values in relation to age. Bone mass acquired at the end of the growth period appears to be more important than bone loss occurring during adult life. The major physiological effect of estrogen is the inhibition of bone resorption. When estrogen transcription possesses binds to the receptors, various genes are activated, and a variety modified. Interleukin 6 (IL-6) stimulates bone resorption, and estrogen blocks osteoblast synthesis of IL-6. Estrogen may also antagonize the IL-6 receptors. Additionally, estrogen inhibits bone resorption by inducing small but cumulative changes in multiple estrogen-dependent regulatory factors including TNF-α and the OPG/RANKL/RANK system. Review on existing data including information about new estrogen-free contraceptives. All progestins exert activity through binding to specific progesterone receptors; hereby, three different groups of progestins exist: pregnanes, gonanes, and estranges. Progestins also comprise specific glucocorticoid, androgen, or mineralocorticoid receptor interactions. Anabolic action of a progestogen may be affected via androgenic, anti-androgenic, or synadrogenic activity. The C 19 nortestosterone class of progestogens is known to bind with more affinity to androgen receptors than the C21 progestins. This article reviews the effect of estrogens and progestogens on bone and presents new data of the currently approved drospirenone-only pill. The use of progestin-only contraceptives leading to an estradiol level between 30 and 50 pg/ml does not seem to lead to an accelerate bone loss.
Topics: Age Factors; Androstenes; Bone Density; Bone Development; Bone Remodeling; Bone Resorption; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Estradiol; Estrogens; Female; Humans; Progestins
PubMed: 31446440
DOI: 10.1007/s00198-019-05103-6 -
Frontiers of Oral Biology 2016Bone is masterfully programmed to repair itself through the coupling of bone formation following bone resorption, a process referred to as coupling. In inflammatory or... (Review)
Review
Bone is masterfully programmed to repair itself through the coupling of bone formation following bone resorption, a process referred to as coupling. In inflammatory or other conditions, the balance between bone resorption and bone formation shifts so that a net bone loss results. This review focuses on four pathologic conditions in which remodeling leads to net loss of bone, postmenopausal osteoporosis, arthritis, periodontal disease, and disuse bone loss, which is similar to bone loss associated with microgravity. In most of these there is an acceleration of the resorptive process due to increased formation of bone metabolic units. This initially leads to a net bone loss since the time period of resorption is much faster than the time needed for bone formation that follows. In addition, each of these processes is characterized by an uncoupling that leads to net bone loss. Mechanisms responsible for increased rates of bone resorption, i.e. the formation of more bone metabolic units, involve enhanced expression of inflammatory cytokines and increased expression of RANKL. Moreover, the reasons for uncoupling are discussed which range from a decrease in expression of growth factors and bone morphogenetic proteins to increased expression of factors that inhibit Wnt signaling.
Topics: Arthritis; Biomechanical Phenomena; Bone Diseases; Bone Remodeling; Bone Resorption; Humans; Inflammation Mediators; Osteogenesis; Osteoporosis, Postmenopausal; Periodontal Diseases; Weightlessness
PubMed: 26599114
DOI: 10.1159/000351896 -
Bone Dec 2020Proper bone remodeling necessarily requires that osteoblasts reconstruct the bone that osteoclasts have resorbed. However, the cellular events connecting resorption to... (Review)
Review
Proper bone remodeling necessarily requires that osteoblasts reconstruct the bone that osteoclasts have resorbed. However, the cellular events connecting resorption to reconstruction have remained poorly known. The consequence is a fragmentary understanding of the remodeling cycle where only the resorption and formation steps are taken into account. New tools have recently made possible to elucidate how resorption shifts to formation, thereby allowing to comprehend the remodeling cycle as a whole. This new knowledge is reviewed herein. It shows how teams of osteoclasts and osteoblast lineage cells are progressively established and how they are subjected therein to reciprocal interactions. Contrary to the common view, osteoclasts and osteoprogenitors are intermingled on the eroded surfaces. The analysis of the resorption and cell population dynamics shows that osteoprogenitor cell expansion and resorption proceed as an integrated mechanism; that a threshold cell density of osteoprogenitors on the eroded surface is mandatory for onset of bone formation; that the cell initiating osteoprogenitor cell expansion is the osteoclast; and that the osteoclast therefore triggers putative osteoprogenitor reservoirs positioned at proximity of the eroded bone surface (bone lining cells, canopy cells, pericytes). The interplay between magnitude of resorption and rate of cell expansion governs how soon bone reconstruction is initiated and may determine uncoupling and permanent bone loss if a threshold cell density is not reached. The clinical perspectives opened by these findings are discussed.
Topics: Bone Remodeling; Bone Resorption; Bone and Bones; Humans; Osteoblasts; Osteoclasts; Osteogenesis
PubMed: 32919109
DOI: 10.1016/j.bone.2020.115628 -
Calcified Tissue International May 2018Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder that occurs in patients with psoriasis and predominantly affects musculoskeletal structures, skin, and... (Review)
Review
Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder that occurs in patients with psoriasis and predominantly affects musculoskeletal structures, skin, and nails. The etiology of PsA is not well understood but evidence supports an interplay of genetic, immunologic, and environmental factors which promote pathological bone remodeling and joint damage in PsA. Localized and systemic bone loss due to increased activity of osteoclasts is well established in PsA based on animal models and translational studies. In contrast, the mechanisms responsible for pathological bone remodeling in PsA remain enigmatic although new candidate molecules and pathways have been identified. Recent reports have revealed novel findings related to bone erosion and pathologic bone formation in PsA. Many associated risk factors and contributing molecular mechanisms have also been identified. In this review, we discuss new developments in the field, point out unresolved questions regarding the pathogenetic origins of the wide array of bone phenotypes in PsA, and discuss new directions for investigation.
Topics: Animals; Arthritis, Psoriatic; Bone Remodeling; Bone Resorption; Bone and Bones; Humans; Osteoclasts; Osteoprotegerin
PubMed: 29330560
DOI: 10.1007/s00223-017-0380-2 -
Anatomical Record (Hoboken, N.J. : 2007) Jun 2022Histomorphometric analysis of human cortical bone has documented the occurrence of secondary osteon variants. These include drifting osteons which form tails as they...
Histomorphometric analysis of human cortical bone has documented the occurrence of secondary osteon variants. These include drifting osteons which form tails as they move erratically through the cortex and Type II osteons which show partial resorption and redeposition within the cement line of the osteon. Little is known about the biological significance of these variants. Prior studies suggested correlations with age, biomechanics, diet, and mineral homeostasis. No study has yet tested for osteon variant associations with static measures of bone remodeling. In this study, thin sections (n = 112) of the posterior femur representing a late English Medieval adult human osteological collection, subdivided by age, sex, and socio-economic status, were examined to determine whether remodeling indicators reconstructed from osteon parameters (area, diameter, area ratios) and densities differed between categories of presence or absence of Type II and drifting osteon variants. Of the 112 sections, 33 presented with Type II osteons, and 38 had drifting osteons. Sporadic statistically significant results were identified. Haversian canal:osteon area ratio differed (p = 0.017) with Type II osteon presence, Type II osteons were more prevalent in males than females (p = 0.048), and drifting osteons were associated with smaller osteon (p = 0.049) and Haversian canal area (p = 0.05). These results may be explained through some biological (sex) and social (status) processes such as a period of physiological recovery (e.g., following lactation, malnutrition). However, the general lack of consistent relationships between osteon variants and remodeling indicators suggests they occur as a result of natural variation.
Topics: Adult; Bone Remodeling; Bone and Bones; Cortical Bone; Female; Femur; Haversian System; Humans; Male
PubMed: 33890727
DOI: 10.1002/ar.24646