Update on the Role of Glucocorticoid Signaling in Osteoblasts and Bone Marrow Adipocytes During Aging

Bensreti, Husam; Alhamad, Dima W.; Gonzalez, Alejandro Marrero; Pizarro-Mondesir, Manuel; Bollag, Wendy B.; Isales, Carlos M.; McGee‐Lawrence, Meghan E.

doi:10.1007/s11914-022-00772-5

Cited by 9 publications

(4 citation statements)

References 155 publications

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“…In general, an inverse relationship exists between BMAT volume and bone mass, including in patients with anorexia nervosa ( 48 – 50 ). Together these results suggest that excess GC during CR may lead to increased BMAT and subsequent bone loss ( 51 , 52 ). Indeed, work from Pierce et al.…”

Section: Discussionmentioning

confidence: 74%

Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction

Schill,

Visser,

Ashby

et al. 2024

Front. Endocrinol.

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IntroductionUnlike white adipose tissue depots, bone marrow adipose tissue (BMAT) expands during caloric restriction (CR). Although mechanisms for BMAT expansion remain unclear, prior research suggested an intermediary role for increased circulating glucocorticoids. MethodsIn this study, we utilized a recently described mouse model (BMAd-Cre) to exclusively target bone marrow adipocytes (BMAds) for elimination of the glucocorticoid receptor (GR) (i.e. Nr3c1) whilst maintaining GR expression in other adipose depots. ResultsMice lacking GR in BMAds (BMAd-Nr3c1-/-) and control mice (BMAd-Nr3c1+/+) were fed ad libitum or placed on a 30% CR diet for six weeks. On a normal chow diet, tibiae of female BMAd-Nr3c1-/- mice had slightly elevated proximal trabecular metaphyseal bone volume fraction and thickness. Both control and BMAd-Nr3c1-/- mice had increased circulating glucocorticoids and elevated numbers of BMAds in the proximal tibia following CR. However, no significant differences in trabecular and cortical bone were observed, and quantification with osmium tetroxide and μCT revealed no difference in BMAT accumulation between control or BMAd-Nr3c1-/- mice. Differences in BMAd size were not observed between BMAd-Nr3c1-/- and control mice. Interestingly, BMAd-Nr3c1-/- mice had decreased circulating white blood cell counts 4 h into the light cycle.DiscussionIn conclusion, our data suggest that eliminating GR from BMAd has minor effects on bone and hematopoiesis, and does not impair BMAT accumulation during CR.

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Section: Discussionmentioning

confidence: 74%

Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction

Schill,

Visser,

Ashby

et al. 2024

Front. Endocrinol.

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“…HCQ is a standard therapy, which is currently the major long-term treatment recommended for all patients with SLE barring limitations or side effects. It reduces SLE activity, particularly in mild and moderate illness, avoid disease flare-ups, and reduce the long-term requirement for glucocorticoids (Bensreti et al, 2022). We therefore intended to compare the immunomodulatory effects of DW with that of the HCQ and Dex drug.…”

Section: Immunomodulation By Dw Treatment Is Similar To That Of Stand...mentioning

confidence: 99%

Autoimmunity and clinical pathology amelioration in SLE by Dexamethasone primed Mesenchymal Stem Cell derived conditioned media

Priya,

Rawat,

Das

et al. 2024

Preprint

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This study proposes a novel approach, utilizing cell-free dexamethasone (Dex) primed Whartons jelly mesenchymal stem cells derived conditioned media (DW), offering improved efficacy, simplicity, and alternative medicine for addressing complications associated with systemic lupus erythematosus (SLE). This study explores the immunomodulatory effects of DW treatment on immune cell populations in SLE patients and a pristane-induced lupus (PIL) mouse model. DW induces significant expansion of Tregs, Bregs, suppressing Th17, double-negative T cells, and inflammatory neutrophils through modulating IL-10 and IL-17A production. Comparisons with the standard drug hydroxychloroquine reveal similar effects, suggesting TGF beta; pathway mediation in DW’s actions. Compared with the immunosuppressive drug Dex, DW better attenuated autoantibody production, increased anti-inflammatory cytokines and maintained a balanced Th17/Treg ratio. In the preclinical in vivo studies, DW exhibits therapeutic efficacy, reducing mortality, preventing proteinuria, and reversing limb inflammation, seizure and alopecia. Organ specific evaluations using advanced live imaging or histopathological analysis highlighted DW’s protective effects on kidneys, liver, lungs, heart, and spleen. This provided insight into the immunomodulatory benefits of DW at various levels and suggested that it could be a potential therapeutic avenue for managing complications related to SLE.

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“…Osteogenesis is tightly regulated by mechanical and biochemical signaling pathways [ 18 ]. During osteogenesis, the sequential differentiation occurs in osteoblast lineage cells, including mesenchymal stem cells (MSCs), osteoprogenitors, pre-osteoblasts, osteoblasts, and osteocytes [ 16 , 17 , 19 , 20 , 21 , 22 ]. Osteoblasts secrete the organic matrix osteoid, which is subsequently calcified to form the bone.…”

Section: Osteogenesis and The Differentiation Of Osteoblast Lineage C...mentioning

confidence: 99%

The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis

Liu,

Wang,

Zhang

et al. 2023

IJMS

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Bones are constantly exposed to mechanical forces from both muscles and Earth’s gravity to maintain bone homeostasis by stimulating bone formation. Mechanotransduction transforms external mechanical signals such as force, fluid flow shear, and gravity into intracellular responses to achieve force adaptation. However, the underlying molecular mechanisms on the conversion from mechanical signals into bone formation has not been completely defined yet. In the present review, we provide a comprehensive and systematic description of the mechanotransduction signaling pathways induced by mechanical stimuli during osteogenesis and address the different layers of interconnections between different signaling pathways. Further exploration of mechanotransduction would benefit patients with osteoporosis, including the aging population and postmenopausal women.

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Update on the Role of Glucocorticoid Signaling in Osteoblasts and Bone Marrow Adipocytes During Aging

Cited by 9 publications

References 155 publications

Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction

Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction

Autoimmunity and clinical pathology amelioration in SLE by Dexamethasone primed Mesenchymal Stem Cell derived conditioned media

The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis

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