BMP3b regulates bone mass by inhibiting BMP signaling.

Bone morphogenetic protein 3b (BMP3b), also known as growth differentiation factor 10 (GDF10), is a non-osteogenic BMP highly expressed in the skeleton. Although in vitro studies have shown that BMP3b suppresses osteoblast differentiation, the physiological role of BMP3b in regulating bone mass in vivo remains unknown. Here, we show that BMP3b deletion in mice leads to a high bone mass phenotype via an unexpected novel mechanism involving de-repression of canonical BMP/Smad signaling.

KIF22 regulates mitosis and proliferation of chondrocyte cells.

Point mutations in have been linked to spondyloepimetaphyseal dysplasia with joint laxity, type 2 (SEMDJL2). Skeletal features of SEMDJL2 include short stature and joint laxity. Mechanisms underlying these limb abnormalities are unknown.

Dietary restriction plus exercise change gene expression of Cxcl12 abundant reticular cells in female mice.

Introduction: Low energy availability due to excessive exercise lowers bone mass and impairs various physiological functions, including immunity and hematopoiesis. We focused on Cxcl12 abundant reticular (CAR) cells, which are bone marrow mesenchymal stem cells and are essential for the maintenance of hematopoietic and immune cells in bone marrow. We examine the functional changes in CAR cells resulting from dietary restriction combined with exercise.

Bub1 suppresses inflammatory arthritis-associated bone loss in mice through inhibition of TNFα-mediated osteoclastogenesis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by synovitis, bone and cartilage destruction, and increased fracture risk with bone loss. Although disease-modifying antirheumatic drugs have dramatically improved clinical outcomes, these therapies are not universally effective in all patients because of the heterogeneity of RA pathogenesis. Therefore, it is necessary to elucidate the molecular mechanisms underlying RA pathogenesis, including associated bone loss, in order to identify novel therapeutic targets.

Cell-specific functions of androgen receptor in skeletal muscles.

Androgens play a vital role not only in promoting the development of male sexual characteristics but also in exerting diverse physiological effects, including the regulation of skeletal muscle growth and function. Given that the effects of androgens are mediated through androgen receptor (AR) binding, an understanding of AR functionality is crucial for comprehending the mechanisms of androgen action on skeletal muscles. Drawing from insights gained using conditional knockout mouse models facilitated by Cre/loxP technology, we review the cell-specific functions of AR in skeletal muscles.

The H3K9 demethylase plant homeodomain finger protein 2 regulates interleukin 4 production in CD4 T cells.

CD4 T cells play a key role in the immune response via their differentiation into various helper T cell subsets that produce characteristic cytokines. Epigenetic changes in CD4 T cells are responsible for cytokine production in these subsets, although the exact molecular mechanisms remain unclear. Therefore, we investigated the effects of plant homeodomain finger protein 2 (PHF2), a histone H3K9 demethylase, on cytokine production in CD4 T cells using T cell-specific Phf2-conditional knockout (cKO) mice in this study.

Centrosome clustering control in osteoclasts through CCR5-mediated signaling.

Osteoclasts uniquely resorb calcified bone matrices. To exert their function, mature osteoclasts maintain the cellular polarity and directional vesicle trafficking to and from the resorbing bone surface. However, the regulatory mechanisms and pathophysiological relevance of these processes remain largely unexplored.

Establishment of a uniform histological evaluation method for early stage osteophytes in the destabilization of the medial meniscus mouse model.

Background: Osteophyte formation is attracting attention as an early-stage pathology of knee osteoarthritis (OA). Although osteophyte formation is understood as a defense response to joint instability, its role and impact on OA remain largely unknown. Many studies have been conducted using the surgical destabilization of the medial meniscus (DMM) mouse model, but there are few standard evaluation methods, especially in the histological evaluation of early-stage osteophytes.

Lenalidomide derivatives and proteolysis-targeting chimeras for controlling neosubstrate degradation.

Lenalidomide, an immunomodulatory drug (IMiD), is commonly used as a first-line therapy in many haematological cancers, such as multiple myeloma (MM) and 5q myelodysplastic syndromes (5q MDS), and it functions as a molecular glue for the protein degradation of neosubstrates by CRL4. Proteolysis-targeting chimeras (PROTACs) using IMiDs with a target protein binder also induce the degradation of target proteins. The targeted protein degradation (TPD) of neosubstrates is crucial for IMiD therapy.

Ingestion of a collagen peptide containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine reduces advanced glycation end products levels in the skin and subcutaneous blood vessel walls: a randomized, double-blind, placebo-controlled study.

In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. A total of 31 individuals aged 47-87 years were randomly assigned to receive either 5 g/day of fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study.

Crosstalk between synovial macrophages and fibroblasts in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation of joints. Abnormally activated cells such as synovial macrophages and synovial fibroblasts induce RA pathogenesis and ultimately joint destruction. Since macrophages can change their own characteristics depending on the microenvironmental condition, it has been suggested that activation and remission of RA are regulated by crosstalk between synovial macrophages and other cells.

LIM1 contributes to the malignant potential of endometrial cancer.

Introduction: The incidence of endometrial cancer (EC) has been increasing worldwide. However, because there are limited chemotherapeutic options for the treatment of EC, the prognosis of advanced-stage EC is poor.

Methods: Gene expression profile datasets for EC cases registered in The Cancer Genome Atlas (TCGA) was reanalyzed.

Isolation and Culture of Primary Synovial Macrophages and Fibroblasts from Murine Arthritis Tissue.

Rheumatoid arthritis is an autoimmune disease that leads to chronic inflammation of joints. Synovial macrophages and synovial fibroblasts have central roles in the pathogenesis of rheumatoid arthritis. It is important to understand the functions of both cell populations to reveal the mechanisms underlying pathological progression and remission in inflammatory arthritis.

Effect of hormonal therapy on the otoconial changes caused by estrogen deficiency.

Benign paroxysmal positional vertigo (BPPV) is associated with menopause and/or osteopenia. Morphological changes in the otoconial layer have been reported after ovariectomy (OVX). Moreover, hormone replacement therapy decreases BPPV risk.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model.

Deletion of Tfam in Prx1-Cre expressing limb mesenchyme results in spontaneous bone fractures.

Introduction: Osteoblasts require substantial amounts of energy to synthesize the bone matrix and coordinate skeleton mineralization. This study analyzed the effects of mitochondrial dysfunction on bone formation, nano-organization of collagen and apatite, and the resultant mechanical function in mouse limbs.

Materials And Methods: Limb mesenchyme-specific Tfam knockout (Tfam;Prx1-Cre: Tfam-cKO) mice were analyzed morphologically and histologically, and gene expressions in the limb bones were assessed by in situ hybridization, qPCR, and RNA sequencing (RNA-seq).

Induction of iPSC-derived Prg4-positive cells with characteristics of superficial zone chondrocytes and fibroblast-like synovial cells.

Background: Lubricin, a proteoglycan encoded by the PRG4 gene, is synthesised by superficial zone (SFZ) chondrocytes and synovial cells. It reduces friction between joints and allows smooth sliding of tendons. Although lubricin has been shown to be effective against osteoarthritis and synovitis in animals, its clinical application remains untested.

Reduced dynamic loads due to hip dislocation induce acetabular cartilage degeneration by IL-6 and MMP3 via the STAT3/periostin/NF-κB axis.

Developmental dysplasia of the hip (DDH) is characterized by anatomical abnormalities of the hip joint, ranging from mild acetabular dysplasia to hip subluxation and eventually dislocation. The mechanism underlying the cartilage degeneration of the hip joints exposed to reduced dynamic loads due to hip dislocation remains unknown. We established a rodent hip dislocation (disarticulation; DA) model of DDH (DA-DDH rats and mice) by swaddling.

Epigenetic regulator UHRF1 orchestrates proinflammatory gene expression in rheumatoid arthritis in a suppressive manner.

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation with aberrant epigenetic alterations, eventually leading to joint destruction. However, the epigenetic regulatory mechanisms underlying RA pathogenesis remain largely unknown. Here, we showed that ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is a central epigenetic regulator that orchestrates multiple pathogeneses in RA in a suppressive manner.

Uhrf1 governs the proliferation and differentiation of muscle satellite cells.

DNA methylation is an essential form of epigenetic regulation responsible for cellular identity. In muscle stem cells, termed satellite cells, DNA methylation patterns are tightly regulated during differentiation. However, it is unclear how these DNA methylation patterns affect the function of satellite cells.

Focal atrial tachycardia originating from the pulmonary vein with onset later than 3 years of age might have a better prognosis, possibly converting in adolescence.

Two cases of focal atrial tachycardia probably originating from the pulmonary vein with onset later than 3 years of age are presented. Both cases had associated variable atrioventricular conduction and showed no signs of heart failure, and they converted to sinus rhythm at the time of puberty. In cases of focal atrial tachycardia originating from the pulmonary vein with onset later than 3 years of age, drug therapy may be effective.

Novel animal model of soft tissue tumor due to aberrant hedgehog signaling activation in pericyte lineage.

Pericytes are pluripotent cells that enclose the endothelium of small blood vessels in the whole body. These cells are thought to play a limited role in vascular development and blood pressure regulation; however, current evidence from numerous studies suggests several significant biologic aspects of pericytes in animals. One viewpoint is that pericytes are also known as potential cellular origin of multiple soft tissue tumors.

Histone H3K27 demethylase, Utx, regulates osteoblast-to-osteocyte differentiation.

Osteocytes are master regulators of skeletal homeostasis. However, little is known about the molecular mechanism of their differentiation. Epigenetic regulations, especially H3K27me3 modification, play critical roles in cell differentiation.