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New Insights into Osteoclasts

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Dear Colleagues,

Our skeleton undergoes continuous remodeling throughout life. Remodeling includes bone removal by osteoclasts, which is followed by bone formation by osteoblasts. However, in pathological conditions, this balance between bone resorption and formation is altered, and leads to the development of bone diseases such as osteoporosis, inflammatory arthritis, and cancer-induced bone loss, where excessive osteoclast activity is associated with low bone density and fragility fractures. To treat these conditions current anti-resorptive therapies, where blocking osteoclastogenesis by targeting RANKL (e.g., denosumab), or promoting apoptosis of osteoclasts (e.g., bisphosphonates) likely inhibit osteoclast-osteoblast interaction as well, since osteoclasts are known to release factors that regulate osteoblast activity. Therefore, identifying novel regulators of osteoclast development, e.g., the ones that act at later stages of osteoclastogenesis, while maintain the ability of osteoclasts to differentiate, may keep osteoclast-osteoblast signalling intact within the bone microenvironment. Thus, better understanding of the molecular and cellular mechanisms underlying physiological and pathological bone resorption may lead to the development of novel strategies for the treatment of bone diseases.

This Special Issue entitled “New Insights into Osteoclasts” welcomes original research articles and timely reviews on the molecular mechanisms of osteoclast development and function, with a special focus on pathological bone resorption in diseases associated with excessive bone loss, e.g., osteoporosis, inflammatory arthritis, and tumor-induced bone loss.

Dr. David Gyori
Guest Editor

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Research

16 pages, 3499 KiB

Open AccessArticle

Supplementation with Rare Earth–Chitosan Chelate Improves Tibia Quality, Disease Resistance Capacity, and Performance in Nursery Pigs

by Shaobin Hao, Wenchen Sun, Panting Wei, Huadong Wu, Wei Lu and Yuyong He

Int. J. Mol. Sci. 2025, 26(6), 2409; https://doi.org/10.3390/ijms26062409 - 7 Mar 2025

Viewed by 426

Abstract

The aim of this study was to investigate the effects on the tibia, liver, and gut, and on performance, when supplementing nursery pigs with different levels of rare earth–chitosan chelate (RECC). A total of 80 piglets, weaned at 7.67 ± 0.09 kg, were randomly assigned to groups RECC0 (RECC, 0 mg/kg diet), RECC200 (RECC, 200 mg/kg diet), RECC400 (RECC, 400 mg/kg diet), and RECC600 (RECC, 600 mg/kg diet), with four replicates in each group and five pigs per replicate during a 28 d experiment. Samples of the left hind tibia, serum, and feces were collected for analysis. The results indicated that, compared to pigs from group RECC0, pigs from group RECC200 presented with the following: a longer trabecular perimeter (p < 0.05), a larger trabecular area (p < 0.01), a higher trabecular number (p < 0.05), a smaller degree of trabecular separation (p < 0.01), and a lower number of osteoclasts (p < 0.01) in the tibia; higher abundances of beneficial fecal bacteria such as g_Prevotellaceae_NK3B31_group, g_UCG_005, g_Rikenellaceae_RC9_gut_group, g_Acetitomaculum, g_Glutamicibacter, g_Frisingicoccus, and g_Alistipes; higher (p < 0.01) serum levels of IgM, IgA, IgG, and IL-10; a lower (p < 0.01) serum concentration of TNF-α; a higher (p < 0.05) average daily gain and feed conversion ratio; and a lower (p < 0.01) incidence of diarrhea. The dietary addition of RECC contributes to improvements in tibia quality, gut health, and performance in nursery pigs. Full article

(This article belongs to the Special Issue New Insights into Osteoclasts)

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17 pages, 782 KiB

Open AccessArticle

The VDR rs1544410 and rs11568820 Variants and the Risk of Osteoporosis in the Polish Population

by Adam Kamiński, Anna Bogacz, Joanna Teresa Niezgoda-Nowak, Marta Podralska, Aleksandra Górska, Michał Soczawa and Bogusław Czerny

Int. J. Mol. Sci. 2025, 26(2), 481; https://doi.org/10.3390/ijms26020481 - 8 Jan 2025

Cited by 1 | Viewed by 955

Abstract

Vitamin D affects bone metabolism and calcium-phosphate metabolism. Its deficiency leads to bone mineralization disorders and is the cause of abnormal skeletal development from fetal life to the period of completed skeletal growth. In later periods of life, vitamin D deficiency leads to bone metabolism disorders, i.e., osteoporosis. Disturbance of the balance between osteoblasts responsible for bone formation and osteoclasts associated with bone resorption results in reduced bone mass and bone weakening, and consequently leads to susceptibility to fractures. Analysis of genetic variants of the vitamin D receptor (VDR) concerns their relationship with metabolic bone diseases, and the results of previous studies assessing the relationship of polymorphisms with bone mineral density, fracture risk, or osteoporosis are not clear. Therefore, the aim of our study was to determine the effect of rs1544410 and rs11568820 polymorphisms of the VDR gene on the risk of developing osteoporosis in the Polish population. The study included 197 women with osteoporosis, 98 women with osteopenia, and 147 healthy controls. The real-time PCR method was used to determine the rs1544410 and rs11568820 polymorphisms of the VDR1 gene. Analysis of the results in the group with osteopenia showed that for the rs1544410 polymorphism, heterozygous GA genotypes occurred in 37.8% of the study group and 47.6% of the controls (OR = 0.60; 95%CI: 0.34–1.05), and homozygous AA in 15.3% of the study group and 17.0% of the controls (OR = 0.68; 95%CI: 0.32–1.44) (p = 0.185, AIC = 332.4; AIC—Akaike information criterion). The best model for this variant turned out to be the dominant model OR = 0.62; 95%CI: 0.37–1.04; p = 0.071, AIC = 330.5. In the case of the rs11568820 polymorphism of the VDR gene, the GG genotype was more common in women with osteopenia compared to controls (75.5% vs. 70.1%). Genotypes containing at least one mutant A allele were present in 24.5% of women with osteopenia and 29.9% of controls (OR = 0.76; 95%CI: 0.43–1.36; p = 0.349; AIC = 332.9). Analyzing the rs1544410 polymorphism in women with osteoporosis, the GA genotype was present in 42.1% of the study group and 47.6% of patients with normal bone density (OR = 0.74; 95%CI: 0.46–1.19), and the AA genotype in 15.7% of the study group and 17.0% of controls (OR = 0.78; 95%CI: 0.41–1.46) (p = 0.441). In the case of the rs11568820 polymorphism, the GA genotype occurred in 22.3% of the study subjects and 27.2% of the control patients (OR = 0.76; 95%CI: 0.46–1.25), and the AA genotype in 2.0% of the study subjects and 2.7% of the controls (OR = 0.69; 95%CI: 0.17–2.83) (p = 0.511). For both variants, the model with the lowest AIC value was the dominant model, in which for the rs1544410 variant OR = 0.75; 95%CI: 0.48–1.17; p = 0.203; AIC = 472.0 was obtained, while for rs11568820—OR = 0.75; 95%CI: 0.47–1.22; p = 0.250; AIC = 472.3. The obtained results indicate that the rs1544410 and rs11568820 polymorphisms of the VDR gene do not affect the development of osteoporosis in the Polish population. Full article

(This article belongs to the Special Issue New Insights into Osteoclasts)

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