scholarly journals MECHANISMS IN ENDOCRINOLOGY: Bone marrow adiposity and bone, a bad romance?

2018 ◽  
Vol 179 (4) ◽  
pp. R165-R182 ◽  
Author(s):  
Tareck Rharass ◽  
Stéphanie Lucas
Keyword(s):  
Bone Marrow ◽  
Bone Growth ◽  
Bone Marrow Cells ◽  
Adult Life ◽  
Osteoclast Formation ◽  
Childhood And Adolescence ◽  
Primary Osteoporosis ◽  
Mineral Density ◽  
Paracrine Factors ◽  
Haematopoietic Tissue

Bone marrow adipocytes (BMA-) constitute an original and heterogeneous fat depot whose development appears interlinked with bone status throughout life. The gradual replacement of the haematopoietic tissue by BMA arises in a well-ordered way during childhood and adolescence concomitantly to bone growth and continues at a slower rate throughout the adult life. Importantly, BM adiposity quantity is found well associated with bone mineral density (BMD) loss at different skeletal sites in primary osteoporosis such as in ageing or menopause but also in secondary osteoporosis consecutive to anorexia nervosa. Since BMA and osteoblasts originate from a common mesenchymal stem cell, adipogenesis is considered as a competitive process that disrupts osteoblastogenesis. Besides, most factors secreted by bone and bone marrow cells (ligands and antagonists of the WNT/β-catenin pathway, BMP and others) reciprocally regulate the two processes. Hormones such as oestrogens, glucocorticoids, parathyroid and growth hormones that control bone remodelling also modulate the differentiation and the activity of BMA. Actually, BMA could also contribute to bone loss through the release of paracrine factors altering osteoblast and/or osteoclast formation and function. Based on clinical and fundamental studies, this review aims at presenting and discussing these current arguments that support but also challenge the involvement of BMA in the bone mass integrity.

Reconstitution of the host holobiont in germ-free born male rats acutely increases bone growth and affects marrow cellular content

2021 ◽  
Author(s):  
Piotr J Czernik ◽  
Rachel M. Golonka ◽  
Saroj Chakraborty ◽  
Beng San Yeoh ◽  
Ahmed A Abokor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Bone Growth ◽  
Elevated Serum ◽  
Male Rats ◽  
Bone Lengthening ◽  
Mineral Density ◽  
Germ Free ◽  
Hepatic Expression ◽  
Gut Colonization

Integration of microbiota in a host begins at birth and progresses during adolescence, forming a multidirectional system of physiologic interactions. Here, we present an instantaneous effect of natural, bacterial gut colonization on the acceleration of longitudinal and radial bone growth in germ-free born, 7-week-old male rats. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in the tibia diaphysis. In addition, the number of small in size adipocytes increased, while the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats indicating that not only bone mass but also bone marrow environment is under control of gut microbiota signaling. The changes in bone status paralleled with a positive shift in microbiota composition toward short chain fatty acids (SCFA)-producing microbes and a considerable increase in cecal SCFA concentrations, specifically butyrate. Further, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels. Elevated serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase. Overall, the presented model of conventionalized germ-free rats could be used to study microbiota-based therapeutics for combatting dysbiosis-related bone disorders.

scholarly journals Nox2 Activity Is Required in Obesity-Mediated Alteration of Bone Remodeling

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Md Mizanur Rahman ◽  
Amina El Jamali ◽  
Ganesh V. Halade ◽  
Allal Ouhtit ◽  
Haissam Abou-Saleh ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Marrow ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Bone Marrow Cells ◽  
Bone Marrow Microenvironment ◽  
Ros Generation ◽  
Chow Diet ◽  
Mineral Density ◽  
Marrow Cells

Despite increasing evidence suggesting a role for NADPH oxidases (Nox) in bone pathophysiology, whether Nox enzymes contribute to obesity-mediated bone remodeling remains to be clearly elucidated. Nox2 is one of the predominant Nox enzymes expressed in the bone marrow microenvironment and is a major source of ROS generation during inflammatory processes. It is also well recognized that a high-fat diet (HFD) induces obesity, which negatively impacts bone remodeling. In this work, we investigated the effect of Nox2 loss of function on obesity-mediated alteration of bone remodeling using wild-type (WT) and Nox2-knockout (KO) mice fed with a standard lab chow diet (SD) as a control or a HFD as an obesity model. Bone mineral density (BMD) of mice was assessed at the beginning and after 3 months of feeding with SD or HFD. Our results show that HFD increased bone mineral density to a greater extent in KO mice than in WT mice without affecting the total body weight and fat mass. HFD also significantly increased the number of adipocytes in the bone marrow microenvironment of WT mice as compared to KO mice. The bone levels of proinflammatory cytokines and proosteoclastogenic factors were also significantly elevated in WT-HFD mice as compared to KO-HFD mice. Furthermore, the in vitro differentiation of bone marrow cells into osteoclasts was significantly increased when using bone marrow cells from WT-HFD mice as compared to KO-HFD mice. Our data collectively suggest that Nox2 is implicated in HFD-induced deleterious bone remodeling by enhancing bone marrow adipogenesis and osteoclastogenesis.

scholarly journals The Use of Mushrooms and Spirulina Algae as Supplements to Prevent Growth Inhibition in a Pre-Clinical Model for an Unbalanced Diet

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4316
Author(s):  
Roni Sides ◽  
Shelley Griess-Fishheimer ◽  
Janna Zaretsky ◽  
Astar Shitrit ◽  
Rotem Kalev-Altman ◽  
...  
Keyword(s):  
Dietary Supplements ◽  
Bone Growth ◽  
Positive Impact ◽  
Bone Development ◽  
Harmful Effect ◽  
Ct Scanning ◽  
Childhood And Adolescence ◽  
Mineral Density ◽  
Clinical Model ◽  
Microbiome Composition

Today’s eating patterns are characterized by the consumption of unbalanced diets (UBDs) resulting in a variety of health consequences on the one hand, and the consumption of dietary supplements in order to achieve overall health and wellness on the other. Balanced nutrition is especially crucial during childhood and adolescence as these time periods are characterized by rapid growth and development of the skeleton. We show the harmful effect of UBD on longitudinal bone growth, trabecular and cortical bone micro-architecture and bone mineral density; which were analyzed by micro-CT scanning. Three point bending tests demonstrate the negative effect of the diet on the mechanical properties of the bone material as well. Addition of Spirulina algae or Pleurotus eryngii or Agaricus bisporus mushrooms, to the UBD, was able to improve growth and impaired properties of the bone. 16SrRNA Sequencing identified dysbiosis in the UBD rats’ microbiota, with high levels of pro-inflammatory associated bacteria and low levels of bacteria associated with fermentation processes and bone related mechanisms. These results provide insight into the connection between diet, the skeletal system and the gut microbiota, and reveal the positive impact of three chosen dietary supplements on bone development and quality presumably through the microbiome composition.

scholarly journals The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures.

1996 ◽  
Vol 183 (6) ◽  
pp. 2581-2591 ◽  
Author(s):  
E Romas ◽  
N Udagawa ◽  
H Zhou ◽  
T Tamura ◽  
M Saito ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Osteoclast Formation ◽  
Pcr Analysis ◽  
Dihydroxyvitamin D3 ◽  
Bone Marrow Cultures ◽  
Primary Osteoblasts ◽  
Marrow Cultures

Interleukin (IL)-11 is a multifunctional cytokine whose role in osteoclast development has not been fully elucidated. We examined IL-11 production by primary osteoblasts and the effects of rat monoclonal anti-mouse glycoprotein 130 (gp130) antibody on osteoclast formation, using a coculture of mouse osteoblasts and bone marrow cells. IL-1, TNF alpha, PGE2, parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) similarly induced production of IL-11 by osteoblasts, but IL-6, IL-4, and TGF beta did not. Primary osteoblasts constitutively expressed mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Osteotropic factors did not modulate IL-11R alpha mRNA at 24 h, but steady-state gp130 mRNA expression in osteoblasts was upregulated by 1 alpha,25(OH)2D3, PTH, or IL-1. In cocultures, the formation of multinucleated osteoclast-like cells (OCLs) in response to IL-11, or IL-6 together with its soluble IL-6 receptor was dose-dependently inhibited by rat monoclonal anti-mouse gp130 antibody. Furthermore, adding anti-gp130 antibody abolished OCL formation induced by IL-1, and partially inhibited OCL formation induced by PGE2, PTH, or 1 alpha,25(OH)2D3. During osteoclast formation in marrow cultures, a sequential relationship existed between the expression of calcitonin receptor mRNA and IL-11R alpha mRNA. Osteoblasts as well as OCLs expressed transcripts for IL-11R alpha, as indicated by RT-PCR analysis and in situ hybridization. These results suggest a central role of gp130-coupled cytokines, especially IL-11, in osteoclast development. Since osteoblasts and mature osteoclasts expressed IL-11R alpha mRNA, both bone-forming and bone-resorbing cells are potential targets of IL-11.

scholarly journals MicroRNA-29a represses osteoclast formation and protects against osteoporosis by regulating PCAF-mediated RANKL and CXCL12

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Wei-Shiung Lian ◽  
Jih-Yang Ko ◽  
Yu-Shan Chen ◽  
Huei-Jing Ke ◽  
Chin-Kuei Hsieh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Estrogen Deficiency ◽  
Biomechanical Property ◽  
Mineral Density ◽  
Cxcl12 Expression ◽  
Osteogenic Cells

Abstract Osteoporosis deteriorates bone mass and biomechanical strength, becoming a life-threatening cause to the elderly. MicroRNA is known to regulate tissue remodeling; however, its role in the development of osteoporosis remains elusive. In this study, we uncovered that silencing miR-29a expression decreased mineralized matrix production in osteogenic cells, whereas osteoclast differentiation and pit formation were upregulated in bone marrow macrophages as co-incubated with the osteogenic cells in transwell plates. In vivo, decreased miR-29a expression occurred in ovariectomy-mediated osteoporotic skeletons. Mice overexpressing miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg/OCN) displayed higher bone mineral density, trabecular volume and mineral acquisition than wild-type mice. The estrogen deficiency-induced loss of bone mass, trabecular morphometry, mechanical properties, mineral accretion and osteogenesis of bone marrow mesenchymal cells were compromised in miR-29aTg/OCN mice. miR-29a overexpression also attenuated the estrogen loss-mediated excessive osteoclast surface histopathology, osteoclast formation of bone marrow macrophages, receptor activator nuclear factor-κ ligand (RANKL) and C–X–C motif chemokine ligand 12 (CXCL12) expression. Treatment with miR-29a precursor improved the ovariectomy-mediated skeletal deterioration and biomechanical property loss. Mechanistically, miR-29a inhibited RANKL secretion in osteoblasts through binding to 3′-UTR of RANKL. It also suppressed the histone acetyltransferase PCAF-mediated acetylation of lysine 27 in histone 3 (H3K27ac) and decreased the H3K27ac enrichment in CXCL12 promoters. Taken together, miR-29a signaling in osteogenic cells protects bone tissue from osteoporosis through repressing osteoclast regulators RANKL and CXCL12 to reduce osteoclastogenic differentiation. Arrays of analyses shed new light on the miR-29a regulation of crosstalk between osteogenic and osteoclastogenic cells. We also highlight that increasing miR-29a function in osteoblasts is beneficial for bone anabolism to fend off estrogen deficiency-induced excessive osteoclastic resorption and osteoporosis.

scholarly journals Jun Dimerization Protein 2 (JDP2), a Member of the AP-1 Family of Transcription Factor, Mediates Osteoclast Differentiation Induced by RANKL

2003 ◽  
Vol 197 (8) ◽  
pp. 1029-1035 ◽  
Author(s):  
Reimi Kawaida ◽  
Toshiaki Ohtsuka ◽  
Junichi Okutsu ◽  
Tohru Takahashi ◽  
Yuho Kadono ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Raw264.7 Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Gene Promoters ◽  
Primary Bone ◽  
Primary Bone Marrow ◽  
Marrow Cells

Osteoclasts are multinucleated cells that resorb bones, and are derived from hematopoietic cells of the monocyte/macrophage lineage. The receptor activator of NF-κB ligand (RANKL, also called ODF/TRANCE/OPGL) stimulates both osteoclast differentiation from osteoclast progenitors and activation of mature osteoclasts. To identify genes responsible for osteoclast differentiation, we used a molecular indexing technique. Here, we report a clone of one of these genes whose transcription is induced by soluble RANKL (sRANKL) in both the RAW264.7 cells of the mouse macrophage cell line and the mouse primary bone marrow cells. The predicted protein was found to be a mouse homologue of Jun dimerization protein 2 (JDP2), a member of the AP-1 family of transcription factors, containing a basic region-leucine zipper motif. Transient transfection experiments revealed that overexpression of JDP2 leads to activation of both tartrate-resistant acid phosphatase (TRAP) and cathepsin K gene promoters in RAW264.7 cells. Infection of mouse primary bone marrow cells with retroviruses expressing JDP2-facilitated sRANKL-mediated formation of TRAP-positive multinuclear osteoclasts. Importantly, antisense oligonucleotide to JDP2 strongly suppressed sRANKL-induced osteoclast formation of RAW264.7 cells. Our findings suggest that JDP2 may play an important role in the RANK-mediated signal transduction system, especially in osteoclast differentiation.

scholarly journals Protocatechuic Acid Attenuates Trabecular Bone Loss in Ovariectomized Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Seon-A Jang ◽  
Hae Seong Song ◽  
Jeong Eun Kwon ◽  
Hyun Jin Baek ◽  
Hyun Jung Koo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Trabecular Bone ◽  
Protocatechuic Acid ◽  
Bone Marrow Cells ◽  
Biomechanical Properties ◽  
Primary Osteoporosis ◽  
Nuclear Factor ◽  
Trabecular Bone Loss ◽  
Marrow Cells

Primary osteoporosis is a disease related to excessive bone resorption due to estrogen insufficiency that occurs postmenopause. Protocatechuic acid (PCA), or 3,4-dihydroxybenzoic acid, is a common compound present in numerous plants. Although numerous biological activities of PCA have been identified, its antiosteoporotic function has not been well established. In this study, the antiosteoporotic activity of PCA supplementation was determined in ovariectomized (OVX) female ICR mice at 12 weeks after OVX. The biomechanical properties of a bone were evaluated by microcomputed tomography. The signaling molecules associated with osteoclast differentiation were determined in bone marrow cells through immunoblot or RT-PCR. Oral supplementation with PCA (20 mg/kg/day) significantly ameliorated the OVX-mediated stimulation of osteoclast activity based on decreases in serum levels of receptor activator of nuclear factor κB ligand (RANKL), osteocalcin, and bone alkaline phosphatase and increase in serum osteoprotegerin (each group, n=6; p<0.05). In addition, the OVX-induced decreases in mRNA expression levels of cathepsin K, calcitonin receptor, nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) in bone marrow cells were significantly attenuated (each group, n=6; p<0.05). Finally, the loss of trabecular bone and changes in biomechanical properties of a bone were significantly improved by supplementation with 20 mg/kg PCA (each group, n=6; p<0.05). Collectively, our results show that PCA supplement suppressed trabecular bone loss in OVX mice and therefore might be an effective alternative approach for preventing the progression of postmenopausal osteoporosis.

Vitamin D antagonist, TEI-9647, inhibits osteoclast formation induced by 1α,25-dihydroxyvitamin D3 from pagetic bone marrow cells

2004 ◽  
Vol 89-90 ◽  
pp. 331-334 ◽  
Author(s):  
Seiichi Ishizuka ◽  
Noriyoshi Kurihara ◽  
Daishiro Miura ◽  
Kazuya Takenouchi ◽  
Jillian Cornish ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vitamin D ◽  
Bone Marrow Cells ◽  
Osteoclast Formation ◽  
Dihydroxyvitamin D3 ◽  
Pagetic Bone ◽  
Marrow Cells
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