Sexual Dimorphism in Osteoclasts

Lorenzo, Joseph

doi:10.3390/cells9092086

Cited by 13 publications

(12 citation statements)

References 50 publications

(75 reference statements)

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“…(7) Despite the well-documented observations of a sex-dependent dimorphism in the skeletal phenotype, the mechanisms that underlie these differences are poorly understood. (8) Osteoclasts are the only cells that can efficiently resorb bone. (9,10) They differentiate from multipotential, myeloidlineage precursor cells under the influence of a variety of cytokines and local factors.…”

Section: Introductionmentioning

confidence: 99%

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Sexual Dimorphism in Differentiating Osteoclast Precursors Demonstrates Enhanced Inflammatory Pathway Activation in Female Cells

Mun

Jastrzebski

Kalinowski

et al. 2020

Journal of Bone and Mineral Research

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Sexual dimorphism of the skeleton is well documented. At maturity, the male skeleton is typically larger and has a higher bone density than the female skeleton. However, the underlying mechanisms for these differences are not completely understood. In this study, we examined sexual dimorphism in the formation of osteoclasts between cells from female and male mice. We found that the number of osteoclasts in bones was greater in females. Similarly, in vitro osteoclast differentiation was accelerated in female osteoclast precursor (OCP) cells. To further characterize sex differences between female and male osteoclasts, we performed gene expression profiling of cultured, highly purified, murine bone marrow OCPs that had been treated for 3 days with macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL). We found that 125 genes were differentially regulated in a sex‐dependent manner. In addition to genes that are contained on sex chromosomes, transcriptional sexual dimorphism was found to be mediated by genes involved in innate immune and inflammatory response pathways. Furthermore, the NF‐κB‐NFATc1 axis was activated earlier in female differentiating OCPs, which partially explains the differences in transcriptomic sexual dimorphism in these cells. Collectively, these findings identify multigenic sex‐dependent intrinsic difference in differentiating OCPs, which results from an altered response to osteoclastogenic stimulation. In humans, these differences could contribute to the lower peak bone mass and increased risk of osteoporosis that females demonstrate relative to males. © 2021 American Society for Bone and Mineral Research (ASBMR).

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Section: Introductionmentioning

confidence: 99%

“…( 7 ) Despite the well‐documented observations of a sex‐dependent dimorphism in the skeletal phenotype, the mechanisms that underlie these differences are poorly understood. ( 8 )…”

Section: Introductionmentioning

confidence: 99%

Sexual Dimorphism in Differentiating Osteoclast Precursors Demonstrates Enhanced Inflammatory Pathway Activation in Female Cells

Mun

Jastrzebski

Kalinowski

et al. 2020

Journal of Bone and Mineral Research

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“…Sex is associated with both osteoporosis and NAFLD: osteoporosis or low bone mass is more common in women than in men of similar age; 75 NAFLD has been proposed to be less common in premenopausal women than in men of similar age, whereas postmenopausal women have similar or even higher rates of NAFLD compared with men of similar age. [76][77][78] Therefore, it seems rational that sex may be another determinant of any association between NAFLD and osteoporosis.…”

Section: Sex As a Possible Determinant Of The Association Between Naf...mentioning

confidence: 99%

Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications

Vachliotis

Anastasilakis

Goulas

et al. 2022

Diabetes Obesity Metabolism

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Nonalcoholic fatty liver disease (NAFLD) and osteoporosis are two highly prevalent metabolic diseases. Increasing experimental evidence supports a pathophysiological link between NAFLD and osteoporosis. A key feature could be chronic, low‐grade inflammation, which characterizes NAFLD and possibly affects bone metabolism. In this context, several factors, including but not limited to receptor activator of nuclear factor kappa‐B ligand, osteoprotegerin, osteopontin and osteocalcin, may serve as mediators. In the clinical setting, most but not all epidemiological evidence indicates that NAFLD is associated with lower bone mineral density or osteoporosis in adults. Although an association between NAFLD and osteoporosis has not yet been established, and thus remains speculative, pharmacological considerations already exist. Some of the current and emerging pharmacological options for NAFLD have shown possible anti‐osteoporotic properties (eg, vitamin E, obeticholic acid, semaglutide), while others (eg, pioglitazone, canagliflozin) have been associated with increased risk of fractures and may be avoided in patients with NAFLD and concomitant osteoporosis, especially those at high fracture risk. Conversely, some anti‐osteoporotic medications (denosumab) might benefit NAFLD, while others (raloxifene) might adversely affect it and, consequently, may be avoided in patients with osteoporosis and NAFLD. If an association between NAFLD and osteoporosis is established, a medication that could target both diseases would be a great advancement. This review summarizes the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focuses on treatment considerations derived from this potential association.

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“…In particular, in women undergoing menopause, estrogen manufacture by the ovaries is strongly reduced as is the amount secreted into the blood. In cases of an estrogen deficiency in postmenopausal women, activities of osteoclasts are concurrently elevated . Subsequently, activated osteoclasts functionally accelerate bone resorption, ultimately resulting in disruption of bone remodeling and homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…In cases of an estrogen deficiency in postmenopausal women, activities of osteoclasts are concurrently elevated. 8 Subsequently, activated osteoclasts functionally accelerate bone resorption, ultimately resulting in disruption of bone remodeling and homeostasis. Consequently, osteoporosis takes place due to the loss of bone mass in menopausal women.…”

Section: ■ Introductionmentioning

confidence: 99%

Naringin Improves Osteoblast Mineralization and Bone Healing and Strength through Regulating Estrogen Receptor Alpha-Dependent Alkaline Phosphatase Gene Expression

Chen

Yang

et al. 2021

J. Agric. Food Chem.

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Phytoestrogens are strongly recommended for treating osteoporosis. Our previous study showed that naringin, a citrus flavonoid, can enhance the bone mass in ovariectomized rats. In this study, we further elucidated the mechanisms of naringininduced osteoblast maturation and bone healing. Treatment of human osteoblasts with naringin increased cell viability and proliferation. In parallel, exposure to naringin enhanced translocation of estrogen receptor alpha (ERα) to nuclei and its transactivation activity. Sequentially, naringin induced alkaline phosphatase (ALP) mRNA and protein expression and its enzyme activity. Pretreatment with methylpiperidinopyrazole (MPP), a specific inhibitor of ERα, attenuated naringin-induced augmentations in ERα transactivation activity, ALP gene expression, and cell mineralization. The beneficial effects of naringin were also confirmed in mouse MC3T3-E1 cells. Moreover, administration of mice with a bone defect with naringin increased levels of ERα and ALP in damaged sites and simultaneously enhanced the healing rate and bone strength. Nevertheless, treatment with MPP weakened naringin-triggered expression of ERα and ALP and improved bone healing and mass. Therefore, naringin could improve osteoblast mineralization and bone healing via regulating ERα-dependent ALP gene expression. Naringin can be clinically applied for treatment of osteoporosis-related bone diseases.

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Sexual Dimorphism in Osteoclasts

Cited by 13 publications

References 50 publications

Sexual Dimorphism in Differentiating Osteoclast Precursors Demonstrates Enhanced Inflammatory Pathway Activation in Female Cells

Sexual Dimorphism in Differentiating Osteoclast Precursors Demonstrates Enhanced Inflammatory Pathway Activation in Female Cells

Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications

Naringin Improves Osteoblast Mineralization and Bone Healing and Strength through Regulating Estrogen Receptor Alpha-Dependent Alkaline Phosphatase Gene Expression

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