Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts

Zhang, Lei; Wang, Qinghai; Cheng, Jiaxiang

doi:10.1016/j.jbiosc.2021.02.007

Cited by 58 publications

(51 citation statements)

References 38 publications

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“…Similarly, in osteoclasts exposed to high concentrations of glucose and the rat model of diabetic OP, the expression levels of NLRP3 inflammasome and its related proteins are increased, bone density is reduced, and osteoclast markers are increased. Besides, the overactivated NLRP3 inflammasome can be inhibited by exosomes originating from MSCs (59). It has been reported that the initiation step for NLRP3 inflammasome activation mainly depends on the NF-kB pathway.…”

Section: Nlrp3 Inflammasome Promotes Bone Resorptionmentioning

confidence: 99%

NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

Jiang

Yang

et al. 2021

Front. Endocrinol.

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Osteoporosis is a systemic bone metabolism disease that often causes complications, such as fractures, and increases the risk of death. The nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an intracellular multiprotein complex that regulates the maturation and secretion of Caspase-1 dependent proinflammatory cytokines interleukin (IL)-1β and IL-18, mediates inflammation, and induces pyroptosis. The chronic inflammatory microenvironment induced by aging or estrogen deficiency activates the NLRP3 inflammasome, promotes inflammatory factor production, and enhances the inflammatory response. We summarize the related research and demonstrate that the NLRP3 inflammasome plays a vital role in the pathogenesis of osteoporosis by affecting the differentiation of osteoblasts and osteoclasts. IL-1β and IL-18 can accelerate osteoclast differentiation by expanding inflammatory response, and can also inhibit the expression of osteogenic related proteins or transcription factors. In vivo and in vitro experiments showed that the overexpression of NLRP3 protein was closely related to aggravated bone resorption and osteogenesis deficiency. In addition, abnormal activation of NLRP3 inflammasome can not only produce inflammation, but also lead to pyroptosis and dysfunction of osteoblasts by upregulating the expression of Caspase-1 and gasdermin D (GSDMD). In conclusion, NLRP3 inflammasome overall not only accelerates bone resorption, but also inhibits bone formation, thus increasing the risk of osteoporosis. Thus, this review highlights the recent studies on the function of NLRP3 inflammasome in osteoporosis, provides information on new strategies for managing osteoporosis, and investigates the ideal therapeutic target to treat osteoporosis.

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Section: Nlrp3 Inflammasome Promotes Bone Resorptionmentioning

confidence: 99%

NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

Jiang

Yang

et al. 2021

Front. Endocrinol.

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“…Previous researches have demonstrated that activating MAPK signaling plays a crucial role in inducing osteoblasts differentiation to reduce and prevent osteoporosis, which may be mediated by increasing the expression levels of P-p38 and P-Jun N-terminal kinase (P-JNK) (Gallea et al, 2001;Zhao et al, 2018). Besides, MSC-Exos could suppress the activation of the NLRP3 inflammasome, inhibit the IL-1β and IL-18 secretion, and alleviate the inflammatory response to improve osteoporosis (Zhang et al, 2021a). Moreover, BMSC-Exos enriched with miR-196a could promote osteogenic differentiation (Peng et al, 2021).…”

Section: Improving Osteoporosismentioning

confidence: 99%

Mechanism of Action of Mesenchymal Stem Cell-Derived Exosomes in the Intervertebral Disc Degeneration Treatment and Bone Repair and Regeneration

Liang

Han

Hai

et al. 2022

Front. Cell Dev. Biol.

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Exosomes are extracellular vesicles formed by various donor cells that regulate gene expression and cellular function in recipient cells. Exosomes derived from mesenchymal stem cells (MSC-Exos) perform the regulatory function of stem cells by transporting proteins, nucleic acids, and lipids. Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, and it is characterized by a decreased number of nucleus pulposus cells, extracellular matrix decomposition, aging of the annulus fibrosus, and cartilage endplate calcification. Besides, nutrient transport and structural repair of intervertebral discs depend on bone and cartilage and are closely related to the state of the bone. Trauma, disease and aging can all cause bone injury. However, there is a lack of effective drugs against IDD and bone injury. Recent MSC-Exos fine tuning has led to significant progress in the IDD treatment and bone repair and regeneration. In this review, we looked at the uniqueness of MSC-Exos, and the potential treatment mechanisms of MSC-Exos with respect to IDD, bone defects and injuries.

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“…There are also reports indicating that increased expression of IL-18 [17] and IL-17 in arterial endothelium may lead to the rapid development of atherosclerosis [14]. In addition, IL-18 may link systemic inflammation with pathological bone remodelling in arthritis due to induction of osteoclast formation and accelerated bone resorption [17][18][19][20][21][22]. Therefore, it is justified to undertake research to verify the hypothesis about the role of IL-18 as a potential "keystone" linking increased cardiovascular risk with active inflammation in PsA.…”

Section: Introductionmentioning

confidence: 99%

Associations of IL-18 with Altered Cardiovascular Risk Profile in Psoriatic Arthritis and Ankylosing Spondylitis

Bonek

Kuca-Warnawin

Kornatka

et al. 2022

JCM

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Objective: To investigate the associations of IL-18 serum levels with serum lipids, cardiovascular risk, and disease activity in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with axial (axPsA) and peripheral (perPsA) joint involvement. Methods: 155 adult patients (PsA 61/AS 94) were enrolled in the study. Standard disease activity indices, BASDAI, and ASDAS, were calculated for AS and PsA and DAPSA for PsA. Sera from peripheral blood samples were obtained after night fasting. Serum concentrations of cytokines (IL-18, IL-17) were measured by ELISA, while lipid profile with total cholesterol (TC), triglycerides (TG), low-density cholesterol-(LDL), high-density cholesterol (HDL), and C-reactive protein (CRP) concentrations were determined using routine procedures. The atherogenic index was calculated using the standard formula AI = TC/HDL. Results: Patients with PsA and peripheral joint involvement (perPsA) had significantly higher IL-18 serum levels than axial PsA and AS patients (medians 160 vs. 116 vs. 80 pg/mL). In patients with PsA and in the subgroup with PsA+ ischemic heart disease (IHD), IL-18 positively correlated with atherogenic index (AI) (rho = 0.46 and rho = 0.67, respectively) and TG serum concentrations (rho = 0.4 and rho = 0.675), while negatively with HDL levels (rho= −0.37 and rho= −0.608). In PsA + IHD subgroup IL-18 serum levels correlated positively also with disease activity (DAPSA) (rho = 0.613). Importantly, in patients with perPsA, characterized by the highest IL-18 serum levels, cardiovascular risk, and frequency of both hypertriglyceridemia and IHD, positive correlations between IL-18 and IL-17 (rho = 0.47, p = 0.002), TG (rho = 0.45 p = 0.01) levels and AI (rho = 0.63 p = 0.021) were found. Whereas linear regression models revealed that IL-17, TG concentrations and the tender joint count had an impact on IL-18 Conclusions: We confirmed that patients with perPsA are characterized by a more pronounced proinflammatory and proatherogenic cardiovascular risk profile than patients with axPsA and AS. Importantly our study indicates that in PsA, but not in AS, elevated serum concentration of IL-18 is associated with higher disease activity and proatherogenic lipid profile, leading to a higher cardiovascular risk. Thus, our results point out IL-18 as a critical contributor in these pathological processes and possible therapeutic targets.

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Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts

Cited by 58 publications

References 38 publications

NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

Mechanism of Action of Mesenchymal Stem Cell-Derived Exosomes in the Intervertebral Disc Degeneration Treatment and Bone Repair and Regeneration

Associations of IL-18 with Altered Cardiovascular Risk Profile in Psoriatic Arthritis and Ankylosing Spondylitis

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