Genetic Ablation of p16 Mitigates Premature Osteoporosis Induced by PTHrP Nuclear Localization Sequence and C-terminal Deletion through Inhibition of Cellular Senescence.

Premature osteoporosis due to parathyroid hormone-related peptide (PTHrP) dysfunction presents significant bone health challenges. This study explores the role of p16-mediated cellular senescence in this condition using a Pthrp knock-in (KI) mouse model lacking the nuclear localization sequence and C-terminus of PTHrP. We generated p16⁻⁄⁻KI mice and compared them with wild-type, p16⁻⁄⁻, and KI mice.

Erratum: Transplantation of bone marrow-derived mesenchymal stem cells rescues partially rachitic phenotypes induced by 1,25-Dihydroxyvitamin D deficiency in mice.

[This corrects the article on p. 4382 in vol. 8, PMID: 27830022.

The senolytic agent ABT263 ameliorates osteoporosis caused by active vitamin D insufficiency through selective clearance of senescent skeletal cells.

Background/objective: Active vitamin D insufficiency accelerates the development of osteoporosis, with senescent bone cells and the senescence-associated secretory phenotype (SASP) playing crucial roles. This study aimed to investigate whether the senolytic agent ABT263 could correct osteoporosis caused by active vitamin D insufficiency by selectively clearing senescent cells.

Methods: Bone marrow mesenchymal stem cells (BM-MSCs) from young and aged mice were treated with ABT263 in vitro, and 1,25(OH)D-insufficient (Cyp27b1) mice were administered ABT263 in vivo.

Metformin prevents mandibular bone loss in a mouse model of accelerated aging by correcting dysregulated AMPK-mTOR signaling and osteoclast differentiation.

Background: Age-related mandibular osteoporosis frequently causes loose teeth, difficulty eating, and disfiguration in elders. Bmi1 mice displaying accelerated skeletal aging represent a useful model for testing interventions against premature jaw bone loss. As an anti-aging agent, metformin may ameliorate molecular dysfunction driving osteoporosis pathogenesis.

Nrf2 activation by pyrroloquinoline quinone inhibits natural aging-related intervertebral disk degeneration in mice.

Age-related intervertebral disk degeneration (IVDD) involves increased oxidative damage, cellular senescence, and matrix degradation. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound with strong anti-oxidant capacity. The goal of this study was to determine whether PQQ can prevent aging-related IVDD, and the underlying mechanism.

Chk2 Modulates Bmi1-Deficiency-Induced Renal Aging and Fibrosis via Oxidative Stress, DNA Damage, and p53/TGFβ1-Induced Epithelial-Mesenchymal Transition.

Renal aging may lead to fibrosis and dysfunction, yet underlying mechanisms remain unclear. We explored whether deficiency of the Polycomb protein Bmi1 causes renal aging via DNA damage response (DDR) activation, inducing renal tubular epithelial cell (RTEC) senescence and epithelial-mesenchymal transition (EMT). Bmi1 knockout mice exhibited oxidative stress, DDR activation, RTEC senescence, senescence-associated secretory phenotype (SASP), and age-related fibrosis in kidneys.

Interferon Regulatory Factor 4 (IRF4) Plays a Key Role in Osteoblast Differentiation of Postmenopausal Osteoporosis.

Background: Postmenopausal osteoporosis (PMOP) is a prevalent disease, which features decreased bone mass, bone weakness and deteriorated bone microstructure in postmenopausal women. Although many factors have been revealed to contribute to the occurrence of PMOP, its mechanism remains undefined. This work aimed to identify significant changes in gene expression during PMOP formation and to examine the most valuable differential genes in postmenopausal osteoporosis versus the control group.

LncRNA PTTG3P promotes tumorigenesis and metastasis of NSCLC by binding with ILF3 to maintain mRNA stability and form a positive feedback loop with E2F1.

Non-small cell lung cancer (NSCLC) is a highly lethal disease worldwide. We found the pseudogene-derived lncRNA PTTG3P is upregulated in NSCLC and associated with larger tumor size, advanced staging, and poor prognosis. This study investigated the oncogenic roles and mechanisms of PTTG3P in NSCLC.

Pyrroloquinoline quinone alleviates natural aging-related osteoporosis via a novel MCM3-Keap1-Nrf2 axis-mediated stress response and Fbn1 upregulation.

Age-related osteoporosis is associated with increased oxidative stress and cellular senescence. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound that has strong antioxidant capacity; however, the effect and underlying mechanism of PQQ on aging-related osteoporosis remain unclear. The purpose of this study was to investigate whether dietary PQQ supplementation can prevent osteoporosis caused by natural aging, and the potential mechanism underlying PQQ antioxidant activity.

Sirt1 protects against intervertebral disc degeneration induced by 1,25-dihydroxyvitamin D insufficiency in mice by inhibiting the NF-κB inflammatory pathway.

Background: It has been demonstrated that vitamin D deficiency is associated with an increased risk of patients developing lumbar disc herniation. However, intervertebral disc degeneration caused by active vitamin D deficiency has not been reported. Thus, the purpose of this study was to e investigate the role and mechanism of 1,25-dihydroxyvitamin D (1,25(OH)D) insufficiency in promoting intervertebral disc degeneration.

Chk2 deletion rescues Bmi1 deficiency-induced mandibular osteoporosis by blocking DNA damage response pathway.

Objectives: Bmi1 deficiency has been proved to be able to cause mandibular osteoporosis through suppressing oxidative stress. However, the role of DNA damage response pathway in this pathogenesis had not been well understood. In this study, we investigate whether mandibular osteoporosis induced by Bmi1 deficiency could be rescued by blocked DNA damage response pathway.

The effect of allyl isothiocyanate on chondrocyte phenotype is matrix stiffness-dependent: Possible involvement of TRPA1 activation.

Osteoarthritis (OA) is a chronic joint disease with increasing prevalence. Chondrocytes (CHs) are highly differentiated end-stage cells with a secretory phenotype that keeps the extracellular matrix (ECM) balanced and the cartilage environment stable. Osteoarthritis dedifferentiation causes cartilage matrix breakdown, accounting for one of the key pathogenesis of osteoarthritis.

1,25-Dihydroxyvitamin D Deficiency Accelerates Aging-related Osteoarthritis via Downregulation of Sirt1 in Mice.

Emerging observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, the relationship between vitamin D level and OA and the role of vitamin D supplementation in the prevention of knee OA are controversial. To address these issues, we analyzed the articular cartilage phenotype of 6- and 12-month-old wild-type and 1α(OH)ase mice and found that 1,25(OH)D deficiency accelerated the development of age-related spontaneous knee OA, including cartilage surface destruction, cartilage erosion, proteoglycan loss and cytopenia, increased OARSI score, collagen X and Mmp13 positive chondrocytes, and increased chondrocyte senescence with senescence-associated secretory phenotype (SASP).

17β-estradiol plays the anti-osteoporosis role via a novel ESR1-Keap1-Nrf2 axis-mediated stress response activation and Tmem119 upregulation.

Increased oxidative stress and decreased osteoblastic bone formation contribute to estrogen deficiency-induced osteoporosis. However, the role and mechanism of estrogen-deficiency in regulating oxidative stress and osteoblastic activity remain unclear. Here, we showed that estrogen-deficient bone marrow stromal/stem cells (BMSCs) exhibited impaired capacity to combat stress, characterized by increased oxidative stress, shortened cell survival and reduced osteogenic differentiation and bone formation, which were due to a decrease of nuclear factor erythroid 2-related factor 2 (Nrf2).

Resveratrol suppresses lung cancer by targeting cancer stem-like cells and regulating tumor microenvironment.

Increasing evidence indicate that cancer stem cells (CSCs) are the key driver of tumor initiation and recurrence. The cellular and soluble components of the tumor microenvironment (TME) impact on cancer initiation and progression, such as cytokines and chemokines. Thus, targeting CSCs and TME is a novel anti-cancer approach.

Long non-coding RNA DUXAP10 exerts oncogenic properties in osteosarcoma by recruiting HuR to enhance SOX18 mRNA stability.

Recent studies have demonstrated that several long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of osteosarcoma (OS). However, more lncRNAs and their mechanisms in regulating growth and migration of OS cells remain to be investigated. In this study, we identified an lncRNA called DUXAP10 by analysis of GEO data, which was significantly up-regulated in OS tissues and cell lines.

LncRNA RAD51-AS1 Regulates Human Bone Marrow Mesenchymal Stem Cells via Interaction with YBX1 to Ameliorate Osteoporosis.

Long noncoding RNA (lncRNA) is a new key regulatory molecule in the occurrence of osteoporosis, but its research is still in the primary stage. In order to study the role and mechanism of lncRNA in the occurrence of osteoporosis, we reannotated the GSE35956 datasets, compared and analyzed the differential expression profiles of lncRNAs between bone marrow mesenchymal stem cells (hBMSCs) from healthy and osteoporotic patients, and then screened a lncRNA RAD51-AS1 with low expression in hBMSCs from osteoporotic patients, and its role in the occurrence of osteoporosis has not been studied. We confirmed that the expression level of lncRNA RAD51-AS1 in hBMSCs from patients with osteoporosis was significantly lower than those from healthy donors.

Role of 1,25-dihydroxyvitamin D in alleviating alveolar bone loss and gingival inflammation in ligature-induced periodontitis.

Objectives: The goal of this study was to assess if endogenous 1,25(OH)D deficiency enhanced, whereas exogenous 1,25(OH)D supplementation alleviated alveolar bone loss and gingival inflammation induced by ligature-induced periodontitis.

Methods: A model of ligature-induced experimental periodontitis was generated in wild-type (WT) and Cyp27b1-knockout (KO) mice on a rescue diet (RD), and un-ligated genotype-matched littermates as control, or in WT mice on a normal diet (ND) with vehicle treatment or 1,25(OH)D treatment, and un-ligated WT littermates as control. Alveolar bone mass and turnover, T cell infiltration and inflammatory cytokines in gingival tissues were examined.