Bone mineral as a drug-seeking moiety and a waste dump

Raina, Deepak; Liu, Yang; Jacobson, Otto L P; Tanner, K.E.; Tägil, Magnus; Lidgren, Lars

doi:10.1302/2046-3758.910.bjr-2020-0097.r1

Cited by 14 publications

(14 citation statements)

References 69 publications

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“… 36 However, bone minerals and apatite also serve as a dumping ground for trace elements and drugs, which seriously affects the bone health. 38 Vitamin D3 supplementation decreased the relative abundance of Escherichia Shigella in the upper gastrointestinal tract. 37 Further, Yang et al 39 found that Shigella flexneri could induce robust inflammasome activation in mouse bone marrow macrophages.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota is associated with bone mineral density

Cheng

Wen

Yang

et al. 2021

Bone & Joint Research

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Aims Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD. Methods A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively. Results We detected five, three, and seven candidate gut microbiota-related traits for L1-L4 BMD, total BMD, and femur BMD, respectively, such as genus Dialister (p = 0.004) for L1-L4 BMD, and genus Eisenbergiella (p = 0.046) for total BMD. We also detected two common gut microbiota-related traits shared by L1-L4 BMD, total BMD, and femur total BMD, including genus Escherichia Shigella and genus Lactococcus. Interaction analysis of BMD detected several genes that interacted with gut microbiota, such as phospholipase D1 ( PLD1) and endomucin ( EMCN) interacting with genus Dialister in total BMD, and COL12A1 and Discs Large MAGUK Scaffold Protein 2 ( DLG2) interacting with genus Lactococcus in femur BMD. Conclusion Our results suggest associations between gut microbiota and BMD, which will be helpful to further explore the regulation mechanism and intervention gut microbiota of BMD. Cite this article: Bone Joint Res 2021;10(11):734–741.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota is associated with bone mineral density

Cheng

Wen

Yang

et al. 2021

Bone & Joint Research

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“…Bone is a dynamic tissue, and bone homeostasis is maintained by numerous cells and factors. 34 , 35 GJIC in osteocytes plays a critical role in regulating signal transmission among different bone cells and maintaining bone homeostasis. 6 , 7 , 36 Emerging evidence has shown that osteocyte GJIC is impaired during the ageing process, which is closely associated with elevated levels of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of advanced oxidation protein products contributes to age-related impairment of gap junction intercellular communication in osteocytes of male mice

Lai

Huang

et al. 2022

Bone & Joint Research

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Aims Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Methods Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. Results The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes’ GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. Conclusion Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413–425.

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“…For example, the broadly studied inorganic material mesoporous silica nanoparticles (MSNs) have shown great applicational advantages in antitumor therapy with good stability, high drug loading, and high degree of customization for applicability ( Baek et al, 2015 ). The most common strategy is to use the unique hydroxyapatite component of the bone, the pharmacokinetic profile can be significantly enhanced and potentiate the skeletal deposition of the drug by combining bone affinities with therapeutic agents ( Raina et al, 2020 ). Since 1986, when the concept of “bone targeting” was put forward, bone targeting research has advanced considerably ( Pierce and Waite, 1987 ).…”

Section: Introductionmentioning

confidence: 99%

Bone-Targeted Nanoparticle Drug Delivery System: An Emerging Strategy for Bone-Related Disease

Chen

et al. 2022

Front. Pharmacol.

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Targeted delivery by either systemic or local targeting of therapeutics to the bone is an attractive treatment for various bone metabolism diseases such as osteoporosis, osteoarthritis, osteosarcoma, osteomyelitis, etc. To overcome the limitations of direct drug delivery, the combination of bone-targeted agents with nanotechnology has the opportunity to provide a more effective therapeutic approach, where engineered nanoparticles cause the drug to accumulate in the bone, thereby improving efficacy and minimizing side effects. Here, we summarize the current advances in systemic or local bone-targeting approaches and nanosystem applications in bone diseases, which may provide new insights into nanocarrier-delivered drugs for the targeted treatment of bone diseases. We envision that novel drug delivery carriers developed based on nanotechnology will be a potential vehicle for the treatment of currently incurable bone diseases and are expected to be translated into clinical applications.

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Bone mineral as a drug-seeking moiety and a waste dump

Cited by 14 publications

References 69 publications

Gut microbiota is associated with bone mineral density

Gut microbiota is associated with bone mineral density

Accumulation of advanced oxidation protein products contributes to age-related impairment of gap junction intercellular communication in osteocytes of male mice

Bone-Targeted Nanoparticle Drug Delivery System: An Emerging Strategy for Bone-Related Disease

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