Panaxatriol exerts anti-senescence effects and alleviates osteoarthritis and cartilage repair fibrosis by targeting UFL1.

Introduction: Osteoarthritis (OA), the most common degenerative joint disease, can eventually lead to disability. However, no safe or effective intervention is currently available. Therefore, there is an urgent need to develop effective drugs that reduce cartilage damage and treat OA.

An Hsp70 promoter-based mouse for heat shock-induced gene modulation.

Physical therapy is extensively employed in clinical settings. Nevertheless, the absence of suitable animal models has resulted in an incomplete understanding of the in vivo mechanisms and cellular distribution that respond to physical stimuli. The objective of this research was to create a mouse model capable of indicating the cells affected by physical stimuli.

Cross-sectional studies of the causal link between asthma and osteoporosis: insights from Mendelian randomization and bioinformatics analysis.

Unlabelled: The study, using data from Chongqing, China, and employing Mendelian randomization along with bioinformatics, establishes a causal link between asthma and osteoporosis, beyond glucocorticoid effects. Asthma may contribute to osteoporosis by accelerating bone turnover through inflammatory factors, disrupting the coupling between osteoblasts and osteoclasts, ultimately leading to osteoporosis.

Introduction: Asthma and osteoporosis are prevalent health conditions with substantial public health implications.

A Novel Cargo Delivery System-AnCar-Exo Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances.

IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis.

Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear.

IRE1α regulates the PTHrP-IHH feedback loop to orchestrate chondrocyte hypertrophy and cartilage mineralization.

Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes, in which the Indian hedgehog (IHH) and parathyroid hormone-related protein-parathyroid hormone-1 receptor (PTHrP-PTH1R) feedback loop is crucial. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) branch of the unfolded protein response (UPR) is essential for normal cartilage development. However, the precise role of ER stress effector IRE1α, encoded by endoplasmic reticulum to nucleus signaling 1 (), in skeletal development remains unknown.

Inhibition of aberrant Hif1α activation delays intervertebral disc degeneration in adult mice.

The intervertebral disc (IVD) is the largest avascular tissue. Hypoxia-inducible factors (HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease (DDD) is one of the leading causes of disability, and current therapies are ineffective.

Long term usage of dexamethasone accelerating accelerates the initiation of osteoarthritis via enhancing chondrocyte apoptosis and the extracellular matrix calcification and apoptosis of chondrocytes.

Systemic application of glucocorticoids is an essential anti-inflammatory and immune-modulating therapy for severe inflammatory or autoimmunity conditions. However, its long-term effects on articular cartilage of patients' health need to be further investigated. In this study, we studied the effects of dexamethasone (Dex) on the homeostasis of articular cartilage and the progress of destabilization of medial meniscus (DMM)-induced osteoarthritis (OA) in adult mice.

Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway.

Acquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) of fibroblast growth factor receptor 3 (FGFR3) in Col2 cells promote acquired HO development.

TGF-β/Alk5 signaling prevents osteoarthritis initiation via regulating the senescence of articular cartilage stem cells.

Osteoarthritis (OA) is the most common joint disease. The surface of joint cartilage is a defensive and first affected structure of articular cartilage (AC) during the pathogenesis of OA. Alk5 signaling is critical for maintaining AC homeostasis, however, the role and underlying mechanism for the involvement of Alk5 signaling in the phenotypes of articular cartilage stem cells (ACSCs) at the surface of AC is still unclear.

FGF/FGFR signaling in health and disease.

Growing evidences suggest that the fibroblast growth factor/FGF receptor (FGF/FGFR) signaling has crucial roles in a multitude of processes during embryonic development and adult homeostasis by regulating cellular lineage commitment, differentiation, proliferation, and apoptosis of various types of cells. In this review, we provide a comprehensive overview of the current understanding of FGF signaling and its roles in organ development, injury repair, and the pathophysiology of spectrum of diseases, which is a consequence of FGF signaling dysregulation, including cancers and chronic kidney disease (CKD). In this context, the agonists and antagonists for FGF-FGFRs might have therapeutic benefits in multiple systems.

mutation disrupts chondrogenesis and bone ossification in zebrafish model mimicking CATSHL syndrome partially via enhanced Wnt/β-catenin signaling.

CATSHL syndrome, characterized by camptodactyly, tall stature and hearing loss, is caused by loss-of-function mutations of fibroblast growth factor receptors 3 (FGFR3) gene. Most manifestations of patients with CATSHL syndrome start to develop in the embryonic stage, such as skeletal overgrowth, craniofacial abnormalities, however, the pathogenesis of these phenotypes especially the early maldevelopment remains incompletely understood. Furthermore, there are no effective therapeutic targets for this skeleton dysplasia.

Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway.

Congenital scoliosis (CS) is a complex genetic disorder characterized by vertebral malformations. The precise etiology of CS is not fully defined. Here, we identify that mutation in dual serine/threonine and tyrosine protein kinase (dstyk) lead to CS-like vertebral malformations in zebrafish.

FGFR3 deficiency enhances CXCL12-dependent chemotaxis of macrophages via upregulating CXCR7 and aggravates joint destruction in mice.

Objectives: This study aims to investigate the role and mechanism of FGFR3 in macrophages and their biological effects on the pathology of arthritis.

Methods: Mice with conditional knockout of FGFR3 in myeloid cells (R3cKO) were generated. Gait behaviours of the mice were monitored at different ages.

Rmrp Mutation Disrupts Chondrogenesis and Bone Ossification in Zebrafish Model of Cartilage-Hair Hypoplasia via Enhanced Wnt/β-Catenin Signaling.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive metaphyseal chondrodysplasia characterized by bone dysplasia and many other highly variable features. The gene responsible for CHH is the RNA component of the mitochondrial RNA-processing endoribonuclease (RMRP) gene. Currently, the pathogenesis of osteochondrodysplasia and extraskeletal manifestations in CHH patients remains incompletely understood; in addition, there are no viable animal models for CHH.

Imbalanced development of anterior and posterior thorax is a causative factor triggering scoliosis.

Objective: Scoliosis is a common disease characterized by spinal curvature with variable severities. There is no generally accepted theory about the physical origin of the spinal deformation of scoliosis. The aim of this study was to explore a new hypothesis suggesting that the curvatures in scoliosis may be associated with the imbalance growth between thoracic vertebral column and sternum.

Adeno-Associated Virus-Mediated RNAi against Mutant Alleles Attenuates Abnormal Calvarial Phenotypes in an Apert Syndrome Mouse Model.

Apert syndrome (AS), the most severe form of craniosynostosis, is caused by missense mutations including Pro253Arg(P253R) of fibroblast growth factor receptor 2 (FGFR2), which leads to enhanced FGF/FGFR2-signaling activity. Surgical correction of the deformed skull is the typical treatment for AS. Because of constant maldevelopment of sutures, the corrective surgery is often executed several times, resulting in increased patient challenge and complications.

Loss of in chondrocytes inhibits osteoarthritis by promoting autophagic activity in temporomandibular joint.

Temporomandibular joint osteoarthritis (TMJ OA) is a common degenerative disease with few effective disease-modifying treatments in the clinic. Fibroblast growth factor (FGF) signaling is implicated in articular cartilage homeostasis, but the functional roles of FGFR1 in TMJ OA remain largely unknown. In this study, we report that deletion of in TMJ chondrocytes delayed TMJ OA progression in the age-associated spontaneous OA model and the abnormal dental occlusion OA model.

FGFR3 deficient mice have accelerated fracture repair.

Bone fracture healing is processed through multiple biological stages that partly recapitulates the skeletal development process. FGFR3 is a negative regulator of chondrogenesis during embryonic stage and plays an important role in both chondrogenesis and osteogenesis. We have investigated the role of FGFR3 in fracture healing using unstabilized fracture model and found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis during cartilage callus formation.

Inducible Activation of FGFR2 in Adult Mice Promotes Bone Formation After Bone Marrow Ablation.

Apert syndrome is one of the most severe craniosynostoses, resulting from gain-of-function mutations in fibroblast growth factor receptor 2 (FGFR2). Previous studies have shown that gain-of-function mutations of FGFR2 (S252W or P253R) cause skull malformation of human Apert syndrome by affecting both chondrogenesis and osteogenesis, underscoring the key role of FGFR2 in bone development. However, the effects of FGFR2 on bone formation at the adult stage have not been fully investigated.

Anemonin attenuates osteoarthritis progression through inhibiting the activation of IL-1β/NF-κB pathway.

The osteoarthritis (OA) progression is now considered to be related to inflammation. Anemonin (ANE) is a small natural molecule extracted from various kinds of Chinese traditional herbs and has been shown to inhibiting inflammation response. In this study, we examined whether ANE could attenuate the progression of OA via suppression of IL-1β/NF-κB pathway activation.

Deformed Skull Morphology Is Caused by the Combined Effects of the Maldevelopment of Calvarias, Cranial Base and Brain in FGFR2-P253R Mice Mimicking Human Apert Syndrome.

Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2 mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively.