Osteoarthritis versus psoriasis arthritis: Physiopathology, cellular signaling, and therapeutic strategies.

Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological, cellular, and clinical levels. Rheumatologists have marked them as two entirely distinct arthropathies. Given recent discoveries in disease initiation and progression, potential mechanisms, cellular signaling pathways, and ongoing clinical therapeutics, there are now more opportunities for discovering osteoarthritis drugs.

The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.

Transforming growth factor-βs (TGF-βs) and bone morphometric proteins (BMPs) belong to the TGF-β superfamily and perform essential functions during osteoblast and chondrocyte lineage commitment and differentiation, skeletal development, and homeostasis. TGF-βs and BMPs transduce signals through SMAD-dependent and -independent pathways; specifically, they recruit different receptor heterotetramers and R-Smad complexes, resulting in unique biological readouts. BMPs promote osteogenesis, osteoclastogenesis, and chondrogenesis at all differentiation stages, while TGF-βs play different roles in a stage-dependent manner.

Harnessing tumor immunogenomics: Tumor neoantigens in ovarian cancer and beyond.

Ovarian cancer is a major cause of death among gynecological cancers due to its highly aggressive nature. Immunotherapy has emerged as a promising avenue for ovarian cancer treatment, offering targeted approaches with reduced off-target effects. With the advent of next-generation sequencing, it has become possible to identify genomic alterations that can serve as potential targets for immunotherapy.

Nutritional Status Indices and Monoclonal Gammopathy of Undetermined Significance Risk in the Elderly Population: Findings from the National Health and Nutrition Examination Survey.

Objective: Although several studies have found dietary intake is related to multiple myeloma (MM) and its precursor status risks, the role of one's nutritional status has been ignored and its role in plasma cell neoplasm development is still unclear. This study aimed to explore the relationship between various clinical indices of nutritional status and the risk of monoclonal gammopathy of undetermined significance (MGUS) in the population.

Methods: We selected 9520 participants from the NHANES III and NHANES 1999-2004 studies.

Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders.

Wnt signaling executes an indispensable performance in osteoblast differentiation, bone development, homeostasis, and remodeling. Wnt signals trigger the intracellular Wnt signaling cascade to initiate regulating the implication of β-catenin in the bone environment. Going through the novel discoveries done via high-throughput sequencing technologies on genetic mouse models, we highlighted the significant contribution of Wnt ligands, co-receptors, inhibitors, their related skeletal phenotypes in mouse models and the similar bone disorders clinically observed in human beings.

Identification of key miRNAs in unilateral mastication-induced disruption of cartilage homeostasis.

Objective: The present study identified potentially pivotal miRNAs contributing to chondrogenic differentiation in temporomandibular joint suffering abnormal stress.

Materials And Methods: Sprague-Dawley rats were randomly divided into control and experimental unilateral mastication (EUM) group. Bone micro-structure parameters was detected by micro-CT, and FGF-1 and MMP-1 expression was examined by immunohistochemistry.

Norcantharidin ameliorates estrogen deficient-mediated bone loss by attenuating the activation of extracellular signal-regulated kinase/ROS/NLRP3 inflammasome signaling.

Osteoporosis, characterized by reduced bone mass, aberrant bone architecture, and elevated bone fragility, is driven by a disruption of bone homeostasis between bone resorption and bone formation. However, up to now, no drugs are perfect for osteoporosis treatment due to different defects. In this study, we demonstrated that norcantharidin (NCTD) could inhibit osteoclast formation and bone resorption by attenuating the ERK, ROS and NLRP3 inflammasomes pathways .

Correction: Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways.

[This corrects the article DOI: 10.1371/journal.pgen.

B-cell receptor repertoire sequencing: Deeper digging into the mechanisms and clinical aspects of immune-mediated diseases.

B cells play an essential role in adaptive immunity and are intimately correlated with pleiotropic immune-mediated diseases. Each B cell occupies a unique B cell receptor (BCR), and all BCRs throughout our body form "BCR repertoire." With the development of sequencing technology and coupled bioinformatics, accumulating evidence indicates that BCR repertoire largely varies under physiological and pathological conditions.

Treatment effect of exercise training on post-stroke depression in middle-aged and older adults: A meta-analysis.

Objective: This meta-analytic study examined the effects of exercise training on depressive symptoms in mild stroke patients and the moderating effects of exercise type, therapeutic method, culture, sex, and gross domestic product (GDP) in the patient's country.

Methods: The Metafor package in R was chosen to conduct the meta-analysis, and the quality of each empirical study was evaluated according to the grading system in Cochrane. We included 36 empirical studies and 1477 patients.

ALX1-transcribed LncRNA AC132217.4 promotes osteogenesis and bone healing via IGF-AKT signaling in mesenchymal stem cells.

The osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) is critical for bone formation and regeneration. A high non-/delayed-union rate of fracture healing still occurs in specific populations, implying an urgent need to discover novel targets for promoting osteogenesis and bone regeneration. Long non-coding (lnc)RNAs are emerging regulators of multiple physiological processes, including osteogenesis.

[Tracking Research Progress in the Modulatory Role of Gut Microbiome in Immune Checkpoint Inhibitors Applied in Cancer Treatment].

In recent years, immunotherapy, as an emerging anti-tumor therapy, has shown great potential in the treatment of both solid and hematologic tumors. There is increasing preclinical and clinical evidence linking the composition of gut microbiome with the efficacy as well as adverse effects of immune checkpoint inhibitor anti-tumor therapy. We summarized in this review the modulatory role of the gut microbiome in antitumor therapy with different immune checkpoint inhibitors.

Therapeutic Agents for the Treatment of Temporomandibular Joint Disorders: Progress and Perspective.

Temporomandibular joint disorders (TMD) are a common health condition caused by the structural or functional disorders of masticatory muscles and the temporomandibular joint (TMJ). Abnormal mandibular movement in TMD patients may cause pain, chronic inflammation, and other discomfort, which could be relieved by a variety of drugs through various delivery systems. In this study, we summarized commonly used therapeutic agents in the management of TMD as well as novel bioactive molecules in preclinical stage and clinical trials.

Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways.

Runx1 is highly expressed in osteoblasts, however, its function in osteogenesis is unclear. We generated mesenchymal progenitor-specific (Runx1f/fTwist2-Cre) and osteoblast-specific (Runx1f/fCol1α1-Cre) conditional knockout (Runx1 CKO) mice. The mutant CKO mice with normal skeletal development displayed a severe osteoporosis phenotype at postnatal and adult stages.

Generation of induced pluripotent stem cell line (XDCMHi001-A) from an Ankylosing spondylitis patient with JAK2 mutation.

Heredity is the major factor contributing to the susceptibility to ankylosing spondylitis(AS). Janus kinase 2 (JAK2) has been associated with AS. Urine-derived cells from an AS patient with JAK2 mutation were used to generate induced pluripotent stem cells (iPSCs) with five episomal iPSC reprogramming vectors (pCXLE-hOCT3/4-shp53-F, pCXLE-hSK, pCXLE-hUL, pCXLE-EGFP and pCXWB-EBNA1).

BMP Signaling in the Development and Regeneration of Cranium Bones and Maintenance of Calvarial Stem Cells.

The bone morphogenetic protein (BMP) signaling pathway is highly conserved across many species, and its importance for the patterning of the skeletal system has been demonstrated. A disrupted BMP signaling pathway results in severe skeletal defects. Murine calvaria has been identified to have dual-tissue lineages, namely, the cranial neural-crest cells and the paraxial mesoderm.

Author Correction: Gα13 negatively controls osteoclastogenesis through inhibition of the Akt-GSK3β-NFATc1 signalling pathway.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cbfβ governs osteoblast-adipocyte lineage commitment through enhancing β-catenin signaling and suppressing adipogenesis gene expression.

The mechanism underlying how transcription factors regulate mesenchymal stem cell lineage commitment remains unclear. To determine the role of core-binding factor subunit beta (Cbfβ) in osteoblast lineage commitment, we generated three mouse models by deleting at different osteoblast lineage stages. We demonstrated that the , and mice exhibited severe osteoporosis with substantial accumulation of marrow adipocytes resembling aged bone from enhanced adipogenesis, indicating that mesenchymal stem cells and osteoblasts can be programed and reprogramed, respectively, into adipocytes.

Gα13 negatively controls osteoclastogenesis through inhibition of the Akt-GSK3β-NFATc1 signalling pathway.

Many positive signalling pathways of osteoclastogenesis have been characterized, but negative signalling pathways are less well studied. Here we show by microarray and RNAi that guanine nucleotide-binding protein subunit α13 (Gα13) is a negative regulator of osteoclastogenesis. Osteoclast-lineage-specific Gna13 conditional knockout mice have a severe osteoporosis phenotype.

TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease.

Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells.

Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet-Induced Insulin Resistance.

In the current study, we used muscle-specific TRIB3 overexpressing (MOE) and knockout (MKO) mice to determine whether TRIB3 mediates glucose-induced insulin resistance in diabetes and whether alterations in TRIB3 expression as a function of nutrient availability have a regulatory role in metabolism. In streptozotocin diabetic mice, TRIB3 MOE exacerbated, whereas MKO prevented, glucose-induced insulin resistance and impaired glucose oxidation and defects in insulin signal transduction compared with wild-type (WT) mice, indicating that glucose-induced insulin resistance was dependent on TRIB3. In response to a high-fat diet, TRIB3 MOE mice exhibited greater weight gain and worse insulin resistance in vivo compared with WT mice, coupled with decreased AKT phosphorylation, increased inflammation and oxidative stress, and upregulation of lipid metabolic genes coupled with downregulation of glucose metabolic genes in skeletal muscle.

Chondrocyte-specific knockout of Cbfβ reveals the indispensable function of Cbfβ in chondrocyte maturation, growth plate development and trabecular bone formation in mice.

Despite years of research into bone formation, the mechanisms by which transcription factors specify growth plate development and trabecular bone formation remain unclear and the role of hypertrophic chondrocytes in trabeculae morphogenesis is controversial. To study the role of Core binding factor beta (Cbfβ) in postnatal cartilage development and endochondral bone formation, we generated chondrocyte-specific Cbfβ-deficient mice (Cbfβf/fCol2α1-Cre mice) using floxed alleles of Cbfβ (Cbfβf/f) and Cre driven by the Collagen 2α1 promoter (Col2α1-Cre). Cbfβf/fCol2α1-Cre mice evaded developmental and newborn lethality to survive to adulthood and displayed severe skeletal malformation.