The role of osteoblasts in energy homeostasis

Dirckx, Naomi; Moorer, Megan C.; Clemens, Thomas L.; Riddle, Ryan C.

doi:10.1038/s41574-019-0246-y

Cited by 216 publications

(161 citation statements)

References 191 publications

(244 reference statements)

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“…We will not address the role of the bone in the regulation of physiological functions that are pivotal in the obesity status such as glucose homeostasis, energy metabolism, and appetite control. This side of the cross-talk has been brilliantly discussed elsewhere (15)(16)(17)(18). In brief, the bone is the fourth glucose consuming organ after muscle, liver and adipose tissue, but unlike these tissues, it consumes glucose preferentially trough the aerobic glycolysis.…”

Section: Introductionmentioning

confidence: 99%

The Bones of Children With Obesity

et al. 2020

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Excess adiposity in childhood may affect bone development, ultimately leading to bone frailty. Previous reports showing an increased rate of extremity fractures in children with obesity support this fear. On the other hand, there is also evidence suggesting that bone mineral content is higher in obese children than in normal weight peers. Both adipocytes and osteoblasts derive from multipotent mesenchymal stem cells (MSCs) and obesity drives the differentiation of MSCs toward adipocytes at the expense of osteoblast differentiation. Furthermore, adipocytes in bone marrow microenvironment release a number of pro-inflammatory and immunomodulatory molecules that up-regulate formation and activation of osteoclasts, thus favoring bone frailty. On the other hand, body adiposity represents a mechanical load, which is beneficial for bone accrual. In this frame, bone quality, and structure result from the balance of inflammatory and mechanical stimuli. Diet, physical activity and the hormonal milieu at puberty play a pivotal role on this balance. In this review, we will address the question whether the bone of obese children and adolescents is unhealthy in comparison with normal-weight peers and discuss mechanisms underlying the differences in bone quality and structure. We anticipate that many biases and confounders affect the clinical studies conducted so far and preclude us from achieving robust conclusions. Sample-size, lack of adequate controls, heterogeneity of study designs are the major drawbacks of the existing reports. Due to the increased body size of children with obesity, dual energy absorptiometry might overestimate bone mineral density in these individuals. Magnetic resonance imaging, peripheral quantitative CT (pQCT) scanning and high-resolution pQCT are promising techniques for the accurate estimate of bone mineral content in obese children. Moreover, no longitudinal study on the risk of incident osteoporosis in early adulthood of children and adolescents with obesity is available. Finally, we will address emerging dietary issues (i.e., the likely benefits for the bone health of polyunsaturated fatty acids and polyphenols) since an healthy diet (i.e., the Mediterranean diet) with balanced intake of certain nutrients associated with physical activity remain the cornerstones for achieving an adequate bone accrual in young individuals regardless of their adiposity degree.

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Section: Introductionmentioning

confidence: 99%

The Bones of Children With Obesity

et al. 2020

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“…Although crucial to bone metastasis and creating the metastatic niche, osteoclasts are not the only cell type to participate in bone metastasis, and osteoblasts also play a vital role. Osteoblasts participate in matrix mineralization, which provides strength (hardness) to the bone ( 30 ). Osteoblasts are derived from skeletal bone marrow stromal cells that differentiate into preosteoblasts and secrete numerous factors, including RANKL that directly impact osteoclastogenesis ( Figure 1 , step ③) ( 30 ).…”

Section: Introduction: Cancer Bone Metastasismentioning

confidence: 99%

“…Osteoblasts participate in matrix mineralization, which provides strength (hardness) to the bone ( 30 ). Osteoblasts are derived from skeletal bone marrow stromal cells that differentiate into preosteoblasts and secrete numerous factors, including RANKL that directly impact osteoclastogenesis ( Figure 1 , step ③) ( 30 ). These cells eventually differentiate into mature osteoblasts, which secrete the mineral matrix proteins and mineralize bone ( 30 ).…”

Section: Introduction: Cancer Bone Metastasismentioning

confidence: 99%

Osteocytes and Bone Metastasis

2020

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Bone is the most frequent site of breast cancer and prostate cancer metastasis, and one of the most common sites of metastasis for many solid tumors. Once cancer cells colonize in the bone, it imposes a major clinical challenge for the treatment of the disease, and fatality rates increase drastically. Bone, the largest organ in the body, provides a fertile microenvironment enriched with nutrients, growth factors and hormones, a generous reward for cancer cells. Dependent on cancer type, cancer cells can cause osteoblastic (bone forming) or osteolytic lesions to promote the net resorption and/or release of growth factors from the bone extracellular matrix. These processes activate a “vicious cycle”, leading to disruption of bone integrity and promoting cancer cell growth and migration. Cancer cells influence the bone microenvironment favoring their colonization and growth. In order to metastasize to the bone, cancer cells must first migrate from the site of origin, and once established within the bone, they must overcome the dormant inducing effects of resident cells. If successful, cancer cells can then colonize and continually disrupt bone homeostasis that is primarily maintained by osteocytes, the most abundant bone cell type. For example, it has been shown that exercise induces osteocytes to release anabolic factors that inhibit osteoclast resorptive activity, promote dormancy and the release of anti-cancer factors that inhibit breast cancer cell metastasis. In this review, we will summarize recent research findings and provide mechanistic insights related to the role of osteocytes in osteolytic metastasis.

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“…Macrophage‐derived osteoclasts are large multinucleated cells that degrade the essential components of the bone by massive secretion of acids and proteinases that dissolve the organic matrix (Ponzetti & Rucci, 2019; Zhao, 2018). During normal physiological conditions, bone resorption is reverted and new segments are formed through specialized bone‐forming cells called as osteoblasts (Dirckx, Moorer, Clemens, & Riddle, 2019). An imbalance between the osteoclast/osteoblast population forms the crux of various bone mediated deformities (Li, Chen, Lu, & Yu, 2020; Terashima & Takayanagi, 2019).…”

Section: Introductionmentioning

confidence: 99%

miR‐506‐3p alleviates uncontrolled osteoclastogenesis via repression of RANKL/NFATc1 signaling pathway

Dinesh

Kalaiselvan

Sujitha

et al. 2020

Journal Cellular Physiology

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Bone erosion is the major cause of deformities in autoimmune disease conditions such as osteoporosis and rheumatoid arthritis. Aberrant receptor activator of nuclear factor kappa B ligand (RANKL) secretion in bone disorders have been implicated to promote uncontrolled osteoclast differentiation through the regulation of nuclear factor of activated T cells 1 (NFATc1) transcription factor. This phenomenon is governed by several molecular factors including microRNAs, which are under‐expressed during disease progression. This report focuses on elucidating the molecular mechanism of miR‐506‐3p towards the RANKL/NFATc1 pathway. miR‐506‐3p showed high binding affinity towards NFATc1 (ΔG = −22.4 kcal/mol). Bone marrow‐derived macrophages (BMMs) isolated from rats stimulated with RANKL (100 ng/ml) showed active expression of NFATc1 which differentiated into mature osteoclasts. Moreover, NFATc1 activation resulted in downstream secretion of various bone resorptive enzymes (cathepsin K, carbonic anhydrase II, tartarate acid phosphatase, and matrix metalloproteinase 9) which lead to active bone resorption. However, transfection of miR‐506‐3p resulted in selective repression of NFATc1 inside the cells. This further resulted in the diminished release of bone resorptive enzymes that were essential for the degradation of the bone. Overall, we predict that miR‐506‐3p can be used as a molecular intervention for RANKL/NFATc1 mediated osteoclastogenesis.

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The role of osteoblasts in energy homeostasis

Cited by 216 publications

References 191 publications

The Bones of Children With Obesity

The Bones of Children With Obesity

Osteocytes and Bone Metastasis

miR‐506‐3p alleviates uncontrolled osteoclastogenesis via repression of RANKL/NFATc1 signaling pathway

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