Insights and implications of sexual dimorphism in osteoporosis

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Фев. 18, 2024

Osteoporosis, a metabolic bone disease characterized by low mineral density and deterioration of microarchitecture, has led to high risk fatal osteoporotic fractures worldwide. Accumulating evidence revealed that sexual dimorphism is notable feature osteoporosis, with sex-specific differences in epidemiology pathogenesis. Specifically, females are more susceptible than males while prone disability or death from the disease. To date, sex chromosome abnormalities steroid hormones have been proven contribute greatly osteoporosis regulating functions cells. Understanding its related complications essential for improving treatment strategies tailored women men. This literature review focuses on mechanisms underlying mainly population aging patients, chronic glucocorticoid administration, diabetes. Moreover, we highlight implications developing therapeutics preventive screening approaches Additionally, challenges translating bench research bedside treatments future directions overcome these obstacles will be discussed.

Язык: Английский

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Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss

Cell, Год журнала: 2024, Номер 187(14), С. 3690 - 3711.e19

Опубликована: Июнь 5, 2024

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A with a higher prevalence periodontitis gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice the heterozygous loss-of-function mutation R878H, equivalent to human hotspot R882H. Partial transplantation Dnmt3aR878H/+ bone marrow (BM) cells resulted mutant into both myeloid lymphoid lineages an elevated abundance osteoclast precursors BM osteoclastogenic macrophages periphery. recipient promoted naturally occurring aggravated experimentally induced arthritis, enhanced osteoclastogenesis, IL-17-dependent neutrophil responses, impaired regulatory T cell immunosuppressive activity. and, subsequently, were suppressed by rapamycin treatment. CHIP represents treatable state maladaptive promoting inflammatory loss.

Язык: Английский

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Current perspectives on the multiple roles of osteoclasts: Mechanisms of osteoclast–osteoblast communication and potential clinical implications

eLife, Год журнала: 2024, Номер 13

Опубликована: Апрель 9, 2024

Bone remodeling is a complex process involving the coordinated actions of osteoblasts and osteoclasts to maintain bone homeostasis. While influence on osteoclast differentiation well established, reciprocal regulation by has long remained enigmatic. In past few years, fascinating new role for been unveiled in promoting formation facilitating osteoblast migration sites through number different mechanisms, including release factors from matrix following resorption direct cell–cell interactions. Additionally, considerable evidence shown that can secrete coupling known as clastokines, emphasizing crucial these cells maintaining Due their osteoprotective function, clastokines hold great promise potential therapeutic targets diseases. However, despite long-standing work uncover effect vivo , more substantial efforts are still required decipher mechanisms pathways behind activity order translate them into therapies. This comprehensive review provides insights our evolving understanding highlights significance remodeling, explores treatments diseases suggesting future directions field.

Язык: Английский

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Unraveling the intricacies of osteoclast differentiation and maturation: insight into novel therapeutic strategies for bone-destructive diseases

Experimental & Molecular Medicine, Год журнала: 2024, Номер 56(2), С. 264 - 272

Опубликована: Фев. 1, 2024

Abstract Osteoclasts are the principal cells that efficiently resorb bone. Numerous studies have attempted to reveal molecular pathways leading differentiation and activation of osteoclasts improve treatment prevention osteoporosis other bone-destructive diseases. While cumulative knowledge osteoclast regulatory molecules, such as receptor activator nuclear factor-kB ligand (RANKL) factor activated T 1 (NFATc1), contributes understanding developmental progression osteoclasts, little is known about how discrete steps osteoclastogenesis modify status but not absolute number osteoclasts. The mechanisms involved in maturation those deserve special attention due their potential use establishing a more effective strategy: targeting late-phase while preserving coupled bone formation. Recent shed light on molecules govern maturation, well metabolic changes needed adapt shifting demands. This review outlines current regulation differentiation, adaptation control mechanism. Additionally, this introduces regulate thus minimally impact

Язык: Английский

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The RANK–RANKL–OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer

Medicina, Год журнала: 2023, Номер 59(10), С. 1752 - 1752

Опубликована: Сен. 30, 2023

The RANK-RANKL-OPG system is a complex signaling pathway that plays critical role in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL ligand binds to RANK, receptor expressed on osteoclasts, dendritic cells, T other cells. promotes osteoclast differentiation activation, which leads resorption. OPG decoy inhibits its signaling. In cancer expression often increased, can lead increased resorption the development of metastases. RANKL-neutralizing antibodies, such as denosumab, have been shown be effective treatment skeletal-related events, including osteoporosis or metastases, This review will provide comprehensive overview functions cancer, together with potential therapeutic implications RANK-RANKL for management.

Язык: Английский

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Pathological progression of osteoarthritis: a perspective on subchondral bone

Frontiers of Medicine, Год журнала: 2024, Номер 18(2), С. 237 - 257

Опубликована: Апрель 1, 2024

Язык: Английский

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Development of a BMU-on-a-chip model based on spatiotemporal regulation of cellular interactions in the bone remodeling cycle

Materials Today Bio, Год журнала: 2025, Номер 32, С. 101658 - 101658

Опубликована: Март 14, 2025

Язык: Английский

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ACT001 improves OVX-induced osteoporosis by suppressing the NF-κB/NLRP3 signaling pathway

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Апрель 7, 2025

Язык: Английский

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Pathophysiology of Medication‐Related Osteonecrosis of the Jaw—A Minireview

JBMR Plus, Год журнала: 2023, Номер 7(8)

Опубликована: Июнь 22, 2023

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse effect antiresorptive medications administered for control osseous malignancy, osteoporosis, or other bone metabolic diseases. Despite being reported in literature two decades ago, MRONJ etiology, pathophysiology, and progression remain largely unknown, current nonoperative operative treatment strategies are mostly empirical. Several hypotheses that attempt to explain mechanisms pathogenesis have been proposed. However, none these alone able capture complex mechanistic underpinnings disease. In this minireview, we aim highlight key findings from clinical translational studies propose unifying model MRONJ. We also identify aspects disease process require further investigation suggest areas future research efforts toward calibrating methodologic approaches validating experimental findings. © 2023 The Authors.

Язык: Английский

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Liver-bone crosstalk in non-alcoholic fatty liver disease: Clinical implications and underlying pathophysiology

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 10, 2023

Osteoporosis is a common complication of many types chronic liver diseases (CLDs), such as cholestatic disease, viral hepatitis, and alcoholic disease. Non-alcoholic fatty disease (NAFLD) highly prevalent metabolic affecting almost one third adults around the world, emerging dominant cause CLDs. Liver serves hub for nutrient energy metabolism in body, its crosstalk with other tissues, adipose tissue, heart, brain, has been well recognized. However, much less known about that occurs between bone. Moreover, mechanisms by which CLDs increase risk osteoporosis remain unclear. This review summarizes latest research on liver-bone axis discusses relationship NAFLD osteoporosis. We cover key signaling molecules secreted liver, insulin-like growth factor-1 (IGF-1), fibroblast factor 21 (FGF21), binding protein 1 (IGFBP1), fetuin-A, tumor necrosis factor-alpha (TNF-α), osteopontin (OPN), their relevance to homeostasis bone metabolism. Finally, we consider disordered patients how this disrupts bone, thereby perturbing balance osteoclasts osteoblasts leading or hepatic osteodystrophy (HOD).

Язык: Английский

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