Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant ...source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables, and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 10 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. The reconstruction of bone defects, in fact, is still a challenge and therefore more research is needed; the articles reviewed are meant to identify compounds useful to stimulate d-DSC proliferation and osteogenic differentiation. We only consider the results of the research which is encouraging, assuming that the mentioned compounds are of some importance for bone regeneration.
Functionally Graded Scaffolds (FGSs) are porous biomaterials where porosity changes in space with a specific gradient. In spite of their wide use in bone tissue engineering, possible models that ...relate the scaffold gradient to the mechanical and biological requirements for the regeneration of the bony tissue are currently missing. In this study we attempt to bridge the gap by developing a mechanobiology-based optimization algorithm aimed to determine the optimal graded porosity distribution in FGSs. The algorithm combines the parametric finite element model of a FGS, a computational mechano-regulation model and a numerical optimization routine. For assigned boundary and loading conditions, the algorithm builds iteratively different scaffold geometry configurations with different porosity distributions until the best microstructure geometry is reached, i.e. the geometry that allows the amount of bone formation to be maximized. We tested different porosity distribution laws, loading conditions and scaffold Young's modulus values. For each combination of these variables, the explicit equation of the porosity distribution law-i.e the law that describes the pore dimensions in function of the spatial coordinates-was determined that allows the highest amounts of bone to be generated. The results show that the loading conditions affect significantly the optimal porosity distribution. For a pure compression loading, it was found that the pore dimensions are almost constant throughout the entire scaffold and using a FGS allows the formation of amounts of bone slightly larger than those obtainable with a homogeneous porosity scaffold. For a pure shear loading, instead, FGSs allow to significantly increase the bone formation compared to a homogeneous porosity scaffolds. Although experimental data is still necessary to properly relate the mechanical/biological environment to the scaffold microstructure, this model represents an important step towards optimizing geometry of functionally graded scaffolds based on mechanobiological criteria.
In the last two decades, numerous scientists have highlighted the interactions between bone and immune cells as well as their overlapping regulatory mechanisms. For example, osteoclasts, the ...bone-resorbing cells, are derived from the same myeloid precursor cells that give rise to macrophages and myeloid dendritic cells. On the other hand, osteoblasts, the bone-forming cells, regulate hematopoietic stem cell niches from which all blood and immune cells are derived. Furthermore, many of the soluble mediators of immune cells, including cytokines and growth factors, regulate the activities of osteoblasts and osteoclasts. This increased recognition of the complex interactions between the immune system and bone led to the development of the interdisciplinary osteoimmunology field. Research in this field has great potential to provide a better understanding of the pathogenesis of several diseases affecting both the bone and immune systems, thus providing the molecular basis for novel therapeutic strategies. In these review, we reported the latest findings about the reciprocal regulation of bone and immune cells.
The myokine irisin increases cortical bone mass Colaianni, Graziana; Cuscito, Concetta; Mongelli, Teresa ...
Proceedings of the National Academy of Sciences - PNAS,
09/2015, Letnik:
112, Številka:
39
Journal Article
Recenzirano
Odprti dostop
It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. ...Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 μg kg⁻¹. We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 μg kg⁻¹ per week) cause browning of adipose tissue; this was not seen with low-dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes,OpnandSost,but notUcp1orPparγexpression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulatedAtf4, Runx2, Osx, Lrp5, β-catenin, Alp,andCol1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursorFndc5was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressedFndc5,albeit at low levels. Furthermore, muscle fibers from r-irisin–injected mice displayed enhanced Fndc5 positivity, and irisin inducedFdnc5mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle–bone connectivity.
We previously showed that Irisin, a myokine released from skeletal muscle after physical exercise, plays a central role in the control of bone mass. Here we report that treatment with recombinant ...Irisin prevented bone loss in hind-limb suspended mice when administered during suspension (preventive protocol) and induced recovery of bone mass when mice were injected after bone loss due to a suspension period of 4 weeks (curative protocol). MicroCT analysis of femurs showed that r-Irisin preserved both cortical and trabecular bone mineral density, and prevented a dramatic decrease of the trabecular bone volume fraction. Moreover, r-Irisin protected against muscle mass decline in the hind-limb suspended mice, and maintained the fiber cross-sectional area. Notably, the decrease of myosin type II expression in unloaded mice was completely prevented by r-Irisin administration. Our data reveal for the first time that Irisin retrieves disuse-induced bone loss and muscle atrophy. These findings may lead to development of an Irisin-based therapy for elderly immobile osteoporotic and physically disable patients, and might represent a countermeasure for astronauts subjected to microgravity-induced bone and muscle losses.
Irisin and Secondary Osteoporosis in Humans Zerlotin, Roberta; Oranger, Angela; Pignataro, Patrizia ...
International journal of molecular sciences,
01/2022, Letnik:
23, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Irisin is a peptide secreted by skeletal muscle following exercise that plays an important role in bone metabolism. Numerous experiments in vitro and in mouse models have shown that the ...administration of recombinant irisin promotes osteogenesis, protects osteocytes from dexamethasone-induced apoptosis, prevents disuse-induced loss of bone and muscle mass, and accelerates fracture healing. Although some aspects still need to be elucidated, such as the dose- and frequency-dependent effects of irisin in cell cultures and mouse models, ample clinical evidence is emerging to support its physiological relevance on bone in humans. A reduction in serum irisin levels, associated with an increased risk of osteoporosis and bone fractures, was observed in postmenopausal women and in both men and women during aging, Recently, cohort studies of subjects with secondary osteoporosis showed that these patients have lower circulating levels of irisin, suggesting that this myokine could be a novel marker to monitor bone quality in this disease. Although there are still few studies, this review discusses the emerging data that are highlighting the involvement of irisin in some diseases that cause secondary osteoporosis.
Abstract
Context
Irisin is a hormonelike molecule that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5). It ameliorates bone status and ...muscle atrophy and influences energy homeostasis. PTH exerts several metabolic effects that may interact with the effects of irisin.
Objectives
To test the hypothesis that irisin and PTH mutually affect their biological action, we evaluated FNDC5 mRNA and protein expression in myotubes treated with PTH (1–34) and parathyroid hormone receptor (PTH-r) mRNA expression in osteoblasts treated with r-irisin. To confirm the in vivo impact of PTH on irisin, we compared irisin serum concentrations in postmenopausal women with primary hyperparathyroidism (PHPT) and control subjects.
Design and Intervention
C2C12 myotubes were treated with short-term and continuous 10−10 M teriparatide and MC3T3-E1 osteoblasts with 100 ng/mL r-irisin for 8 hours. In a cross-sectional open-label trial, we enrolled 26 postmenopausal women with PHPT and 31 age-/body mass index (BMI)‒matched control subjects without impairment of calcium/phosphate metabolism.
Results
Teriparatide treatment on myotubes significantly downregulated FNDC5 expression by acting through its own receptor, which in turn activated Erk11/2 phosphorylation. r-Irisin led to a 50% downregulation of PTH-r mRNA expression compared with untreated cells (P < 0.001). Irisin was significantly lower in the PHPT group than in age-/BMI-matched controls (4.5 ± 1.1 vs 12 ± 5.2 µg/mL; P < 0.001). No significant correlation between irisin and bone mineral density or PTH was recorded in the PHPT group.
Conclusion
Preclinical findings suggest the existence of an interplay between PTH and irisin metabolism that seems to be confirmed by the significant reduction of irisin concentration in postmenopausal women with PHPT.
In vitro findings suggest the existence of interplay between PTH and irisin metabolism that seems to be confirmed by a significant reduction in irisin concentration in postmenopausal women with PHPT.
It has been recently demonstrated that exercise activity increases the expression of the myokine Irisin in skeletal muscle, which is able to drive the transition of white to brown adipocytes, likely ...following a phenomenon of transdifferentiation. This new evidence supports the idea that muscle can be considered an endocrine organ, given its ability to target adipose tissue by promoting energy expenditure. In accordance with these new findings, we hypothesized that Irisin is directly involved in bone metabolism, demonstrating its ability to increase the differentiation of bone marrow stromal cells into mature osteoblasts. Firstly, we confirmed that myoblasts from mice subjected to 3 weeks of free wheel running increased Irisin expression compared to nonexercised state. The conditioned media (CM) collected from myoblasts of exercised mice induced osteoblast differentiation in vitro to a greater extent than those of mice housed in resting conditions. Furthermore, the differentiated osteoblasts increased alkaline phosphatase and collagen I expression by an Irisin-dependent mechanism. Our results show, for the first time, that Irisin directly targets osteoblasts, enhancing their differentiation. This finding advances notable perspectives in future studies which could satisfy the ongoing research of exercise-mimetic therapies with anabolic action on the skeleton.
Depression is a psychiatric disorder increasingly diffused worldwide. Evidence suggests that irisin, a myokine secreted by contracting muscle, mediates beneficial effects on several targets, ...including the brain. Here, the potential antidepressant properties of long-term intermittent systemic irisin administration (100 µg/kg/weekly for 1 month) were evaluated in mice by the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). Furthermore, to deepen the molecular pathways underlying irisin treatment, the expression of irisin precursor, neurotrophic/growth factors, and cytokines was analyzed. Irisin treatment significantly decreased the immobility time in the TST and FST, suggesting an antidepressant effect. Additionally, irisin seemed to display an anxiolytic-like effect increasing the time spent in the OFT arena center. These findings were probably due to the modulation of endogenous brain factors as the gene expression of some neurotrophins, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF-1), was upregulated only in irisin-treated mouse brain. Moreover, irisin modulated the expression of some cytokines (IL-1β, IL-4, IL-6, and IL-10). To the best of our knowledge, this is the first study demonstrating that the irisin antidepressant effect may be observed even with a systemic administration in mice. This could pave the way toward intriguing preclinical research in humans.
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