T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone

Pacifici, Roberto

doi:10.1111/nyas.12969

Cited by 64 publications

(59 citation statements)

References 160 publications

(361 reference statements)

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“…Moreover, IL-17 stimulates the release of RANKL by OB and OCy and upregulate RANK expression on OC. Treg exert anti-osteo-clastogenic activity by producing suppressor cytokines, including IL-4, IL-10, and TGF-β [21]. …”

Section: Crosstalk Between the Immune And Bone System: The Immunoskelmentioning

confidence: 99%

“…CD40L also increases the commitment of MSC to the osteoblastic lineage. Through CD80/86 signaling in OCP, T cells suppress OC differentiation [21]. …”

Section: Crosstalk Between the Immune And Bone System: The Immunoskelmentioning

confidence: 99%

“…The catabolic effect of cPTH is mostly mediated by enhanced production of RANKL and decreased production of OPG by OB and stromal cells. The PTH anabolic effect is mediated by Wnt signaling activation: PTH increases β-catenin levels in OB, promotes LRP6 signaling and decreases the production of sclerostin [21]. cPTH stimulates bone cells and immune cells to release growth factors and cytokines, including IL-6 and TNF-α, which induce Th17 cell differentiation and the production of IL-17, that plays a pivotal role in the PTH induced bone loss [21].…”

Section: Crosstalk Between the Immune And Bone System: The Immunoskelmentioning

confidence: 99%

“…The PTH anabolic effect is mediated by Wnt signaling activation: PTH increases β-catenin levels in OB, promotes LRP6 signaling and decreases the production of sclerostin [21]. cPTH stimulates bone cells and immune cells to release growth factors and cytokines, including IL-6 and TNF-α, which induce Th17 cell differentiation and the production of IL-17, that plays a pivotal role in the PTH induced bone loss [21]. TNF-α in turn stimulates OC formation and activity via multiple mechanisms, including increased RANKL production.…”

Section: Crosstalk Between the Immune And Bone System: The Immunoskelmentioning

confidence: 99%

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Osteoimmunology and Beyond

Ginaldi

Martinis²

2016

CMC

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ObjectiveOsteoimmunology investigates interactions between skeleton and immune system. In the light of recent discoveries in this field, a new reading register of osteoporosis is actually emerging, in which bone and immune cells are strictly interconnected. Osteoporosis could therefore be considered a chronic immune mediated disease which shares with other age related disorders a common inflammatory background. Here, we highlight these recent discoveries and the new landscape that is emerging.MethodExtensive literature search in PubMed central.ResultsWhile the inflammatory nature of osteoporosis has been clearly recognized, other interesting aspects of osteoimmunology are currently emerging. In addition, mounting evidence indicates that the immunoskeletal interface is involved in the regulation of important body functions beyond bone remodeling. Bone cells take part with cells of the immune system in various immunological functions, configuring a real expanded immune system, and are therefore variously involved not only as target but also as main actors in various pathological conditions affecting primarily the immune system, such as autoimmunity and immune deficiencies, as well as in aging, menopause and other diseases sharing an inflammatory background.ConclusionThe review highlights the complexity of interwoven pathways and shared mechanisms of the crosstalk between the immune and bone systems. More interestingly, the interdisciplinary field of osteoimmunology is now expanding beyond bone and immune cells, defining new homeostatic networks in which other organs and systems are functionally interconnected. Therefore, the correct skeletal integrity maintenance may be also relevant to other functions outside its involvement in bone mineral homeostasis, hemopoiesis and immunity.

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Section: Crosstalk Between the Immune And Bone System: The Immunoskelmentioning

confidence: 99%

“…CD40L also increases the commitment of MSC to the osteoblastic lineage. Through CD80/86 signaling in OCP, T cells suppress OC differentiation [21]. …”

Section: Crosstalk Between the Immune And Bone System: The Immunoskelmentioning

confidence: 99%

Section: Crosstalk Between the Immune And Bone System: The Immunoskelmentioning

confidence: 99%

Section: Crosstalk Between the Immune And Bone System: The Immunoskelmentioning

confidence: 99%

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Osteoimmunology and Beyond

Ginaldi

Martinis²

2016

CMC

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“…Among the cells of the immune system that regulate bone turnover and the responsiveness of bone cells to calciotropic hormones are bone marrow T lymphocytes [77]. T cells secrete osteoclastogenic cytokines, such as RANKL and TNF-α, as well as factors that stimulate bone formation, one of which is Wnt10b [78]. A significant study demonstrated that the metabolic syndrome and atherosclerosis are linked, since oxidized lipids decrease bone mass by increasing antiosteoblastogenic inflammatory cytokines and decreasing proosteoblastogenic Wnt ligands [79].…”

Section: Bone Mass: Osteopenia and Osteoporosismentioning

confidence: 99%

Chronic stress and body composition disorders: implications for health and disease

Stefanaki

Pervanidou

Boschiero³

et al. 2018

Hormones

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Recent studies have suggested that body composition is key to health and disease. First, fat tissue is a complex, essential, and highly active metabolic and endocrine organ that responds to afferent signals from traditional hormone systems and the central nervous system but also expresses and secretes factors with important endocrine, metabolic, and immune functions. Second, skeletal muscle mass is an important predictor of health in adult life, while severe mass loss has been associated with the frailty of old age. Studies have shown that skeletal muscle is also an important endocrine organ that secretes factors with autocrine, paracrine, or endocrine actions, which have been associated with inflammatory processes. Third, the bone is also a systemic endocrine regulator playing a pivotal role in health and disease. Finally, proper hydration in humans has been neglected as a health factor, especially in adults. Chronic stress and stress hormone hypersecretion alone or associated with distinct disorders, such as anxiety, depression, obesity, metabolic syndrome, autoimmune disorders, type 2 diabetes mellitus, and polycystic ovary syndrome (PCOS), have been associated with psychological and somatic manifestations, typically, increased fat mass, osteosarcopenia/frailty, cellular dehydration, and chronic systemic inflammation. This review aims to provide new insights into the newly developed concept of stress-related osteosarcopenic obesity and its prevention.

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Spatiotemporally Controlled Release of Rho‐Inhibiting C3 Toxin from a Protein–DNA Hybrid Hydrogel for Targeted Inhibition of Osteoclast Formation and Activity

Gačanin

Kovtun

Fischer

et al. 2017

Adv Healthcare Materials

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In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks. The hybrid hydrogel combines advantageous characteristics, including rapid gelation through DNA hybridization under physiological conditions and a self-healing and injectable nature with the possibility of specific loading and spatiotemporally controlled release of active proteins, making it an advanced biomaterial for the local treatment of bone diseases, for example, osteoporosis. The hydrogels are loaded with a recombinant Rho-inhibiting C3 toxin, C2IN-C3lim-G205C. This toxin selectively targets osteoclasts and inhibits Rho-signaling and, thereby, actin-dependent processes in these cells. Application of C2IN-C3lim-G205C toxin-loaded hydrogels effectively reduces osteoclast formation and resorption activity in vitro, as demonstrated by tartrate-resistant acid phosphatase staining and the pit resorption assay. Simultaneously, osteoblast activity, viability, and proliferation are unaffected, thus making C2IN-C3lim-G205C toxin-loaded hybrid hydrogels an attractive pharmacological system for spatial and selective modulation of osteoclast functions to reduce bone resorption.

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T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone

Cited by 64 publications

References 160 publications

Osteoimmunology and Beyond

Osteoimmunology and Beyond

Chronic stress and body composition disorders: implications for health and disease

Spatiotemporally Controlled Release of Rho‐Inhibiting C3 Toxin from a Protein–DNA Hybrid Hydrogel for Targeted Inhibition of Osteoclast Formation and Activity

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