Stat3 Signaling Pathway: A Future Therapeutic Target for Bone-Related Diseases

Article Medicine, Research & Experimental

Osteoinductive activity of bisdemethoxycurcumin and its synergistic protective effect with human amniotic mesenchymal stem cells against ovariectomy-induced osteoporosis mouse model

Jin-Xing Wei et al.

Summary: Bisdeme-thoxycurcumin (BDMC) can stimulate the differentiation of human amniotic mesenchymal stem cells (hAMSCs) into osteoblasts, potentially serving as an effective adjuvant therapy for osteoporosis.

BIOMEDICINE & PHARMACOTHERAPY (2022)

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Article Biochemistry & Molecular Biology

Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation

Xiaoli Xu et al.

Summary: This study reveals that myeloid cell-derived MYDGF plays a positive regulatory role in bone homeostasis by inhibiting bone resorption and promoting bone formation. MYDGF could be a potential novel therapeutic drug for osteoporosis, and bone marrow may be a potential therapeutic target for bone metabolic disorders.

EMBO REPORTS (2022)

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Article Biology

gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes

Nancy Q. Liu et al.

Summary: The study demonstrates the significance of gp130/STAT3 signaling in the development and homeostasis of chondrocytes in the growth plate and articular cartilage. The findings suggest that the deletion of STAT3 or gp130 in chondrocytes can lead to defective chondrocyte proliferation, growth plate fusion, and dysfunction of the articular cartilage. The study also highlights the positive role of IL-6 family cytokines in the skeletal system.

COMMUNICATIONS BIOLOGY (2022)

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Review Pharmacology & Pharmacy

Signal transducer and activator of transcription 3 signaling in tumor immune evasion

Luying Zhang et al.

Summary: The underlying mechanism of tumor immune evasion, particularly the role of STAT3 in promoting tumor cell escape from immune surveillance through regulating autophagy molecules, immune factors, and immunosuppressive cell recruitment, is discussed in this review. The article also highlights the significance of the research on STAT3 signaling and tumor immune evasion in the development of targeted drugs for immunotherapy.

PHARMACOLOGY & THERAPEUTICS (2022)

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Article Engineering, Biomedical

Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant

Ze Lin et al.

Summary: This study demonstrates the use of PD-L1-enriched exosomes for bone fracture repair and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects. The results show that exosomal PD-L1 can inhibit T cell activation and promote osteogenic differentiation of mesenchymal stem cells. Additionally, embedding exosomes in a hydrogel allows for time-released delivery and improves treatment efficacy.

BIOACTIVE MATERIALS (2022)

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Article Engineering, Biomedical

Hypoxic pretreatment of small extracellular vesicles mediates cartilage repair in osteoarthritis by delivering miR-216a-5p

Yuluo Rong et al.

Summary: The study demonstrated that hypoxic pretreatment of small extracellular vesicles effectively protected cartilage from degeneration and slowed down the progression of OA. Through the miR-216a-5p/JAK2/STAT3 pathway, hypoxic pretreatment is promising for optimizing the therapeutic effects of BMSC-derived sEVs.

ACTA BIOMATERIALIA (2021)

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Review Cardiac & Cardiovascular Systems

Regulation of STAT3 and its role in cardioprotection by conditioning: focus on non-genomic roles targeting mitochondrial function

Stefano Comita et al.

Summary: Cardioprotective conditioning strategies such as pre- and post-conditioning maneuvers play a crucial role in stimulating pro-survival pathways like STAT3 for the preservation of cardiac health. The importance of STAT3 as a promoter of metabolic network and its interactions with processes aimed at maintaining mitochondrial functions have been highlighted in understanding cardioprotection phenomena.

BASIC RESEARCH IN CARDIOLOGY (2021)

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Review Cell Biology

STAT3 and its targeting inhibitors in osteosarcoma

Yun Liu et al.

Summary: STAT3, a key protein involved in cell growth, differentiation, and survival, is overexpressed in osteosarcoma and various cancers. Its constitutive activation leads to upregulation of oncogenes, affecting processes such as transformation, proliferation, and metastasis.

CELL PROLIFERATION (2021)

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Article Endocrinology & Metabolism

The JAK inhibitor Tofacitinib inhibits structural damage in osteoarthritis by modulating JAK1/TNF-alpha/IL-6 signaling through Mir-149-5p

Yen-Shuo Chiu et al.

Summary: Research has revealed that miR-149-5p is downregulated in clinical OA samples, contributing to chronic inflammation by increasing TNF-alpha/IL-6 signaling within the synovium and OA progression. Additionally, therapeutic effects of tofacitinib, a JAK inhibitor, were evaluated in in vitro and in vivo OA models, showing potential in suppressing inflammation and restoring miR-149-5p expression.

BONE (2021)

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Review Biochemistry & Molecular Biology

An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage

Alfonso Cordero-Barreal et al.

Summary: Leptin, a adipokine, has significant impact on cartilage metabolism and pathology by inducing the expression of pro-inflammatory molecules and cartilage degenerative enzymes through its signaling pathway involving the long isoform of the leptin receptor (LEPRb). It has been shown that inhibition of leptin signaling can have protective effects in degenerative cartilage diseases such as osteoarthritis, rheumatoid arthritis, and systemic lupus erythematosus. Leptin also plays a key role in increasing the proliferation and activation of immune cells, exacerbating the severity of immune degenerative cartilage diseases.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Lycopene inhibits IL-1β-induced inflammation in mouse chondrocytes and mediates murine osteoarthritis

Jingdi Zhan et al.

Summary: The study demonstrated that Lycopene could inhibit the expression of inflammatory factors, alleviate the degradation of extracellular matrix, and activate the Nrf2/HO-1 pathway to reverse the activations of NF-kappa B and STAT3 signal pathway. The results suggest that Lycopene may be a promising novel drug for OA treatment as it could inhibit the occurrence and development of OA in mice.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2021)

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Article Cell & Tissue Engineering

STAT3 activation by catalpol promotes osteogenesis-angiogenesis coupling, thus accelerating osteoporotic bone repair

Liang Chen et al.

Summary: The study found that catalpol can enhance the osteogenic ability of bone marrow mesenchymal stem cells and promote BMSC-mediated angiogenesis by activating the JAK2/STAT3 signaling pathway. This suggests that catalpol may be an ideal therapeutic agent for the clinical treatment of osteoporotic bone fractures.

STEM CELL RESEARCH & THERAPY (2021)

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Article Cell Biology

Inhibition of nuclear receptor RORα attenuates cartilage damage in osteoarthritis by modulating IL-6/STAT3 pathway

Tongzhou Liang et al.

Summary: Evidence suggests that ROR alpha plays a crucial role in cartilage development and OA pathogenesis by regulating the expression of cartilage matrix components. Blocking ROR alpha can reverse cartilage damage and elevate the expression of cartilage matrix components. Additionally, ROR alpha affects the IL-6/STAT3 signaling pathway, highlighting its potential as a treatment target in OA therapy.

CELL DEATH & DISEASE (2021)

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Article Multidisciplinary Sciences

STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis

Siru Zhou et al.

Summary: The study found that inactivation of STAT3 in osteoblasts can induce AD-HIES-like skeletal defects, while pharmacological activation of STAT3 can rescue this phenotype. STAT3 cooperates with MSX1 to drive osteoblast differentiation, indicating the importance of STAT3 in modulating skeletal development and maintaining bone homeostasis.

NATURE COMMUNICATIONS (2021)

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Article Engineering, Biomedical

被撤回的出版物: Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel (Retracted article. See vol. 7, pg. 1, 2022)

Xiang He et al.

Summary: The prepared Rb-SA/PAAm hydrogels for psoriasis treatment showed good mechanical properties, antibacterial ability, and the ability to alleviate symptoms caused by Imiquimod in mice.

BIOACTIVE MATERIALS (2021)

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Article Pharmacology & Pharmacy

Nitazoxanide, an Antiprotozoal Drug, Reduces Bone Loss in Ovariectomized Mice by Inhibition of RANKL-Induced Osteoclastogenesis

Chang-hong Li et al.

Summary: Nitazoxanide (NTZ) has shown potential in inhibiting osteoclastogenesis and bone loss by modulating the STAT3-NFATc1 signaling pathway. The study found that NTZ suppressed osteoclast formation and activity through inhibition of STAT3 phosphorylation and reduction of NFATc1 expression. NTZ could be a potential alternative treatment for bone destruction-related diseases like osteoporosis.

FRONTIERS IN PHARMACOLOGY (2021)

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Article Pharmacology & Pharmacy

BCI Suppresses RANKL-Mediated Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss

Chenhui Cai et al.

Summary: BCI treatment attenuates osteoclast differentiation and alleviates osteoporosis by inhibiting STAT3 and NF-kappa B signaling pathways, suggesting a potential effective approach for treating osteoporosis.

FRONTIERS IN PHARMACOLOGY (2021)

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Article Pharmacology & Pharmacy

Selective STAT3 Inhibitor Alantolactone Ameliorates Osteoarthritis via Regulating Chondrocyte Autophagy and Cartilage Homeostasis

Wenbin Pei et al.

Summary: In this study, it was found that Alantolactone (ALT) could alleviate IL-1 beta-induced inflammatory responses, protect cartilage from damage, and promote impaired autophagy through inhibiting the STAT3 and NF-kappa B signal pathways, suggesting a promising therapeutic effect for osteoarthritis.

FRONTIERS IN PHARMACOLOGY (2021)

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Article Pharmacology & Pharmacy

Betaine Attenuates Osteoarthritis by Inhibiting Osteoclastogenesis and Angiogenesis in Subchondral Bone

Wang Yajun et al.

Summary: Betaine attenuated OA progression by inhibiting hyperactivated osteoclastogenesis and maintaining microarchitecture in subchondral bone. Additionally, betaine could reorganize the structure of subchondral bone and inhibit abnormal angiogenesis.

FRONTIERS IN PHARMACOLOGY (2021)

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Review Biochemistry & Molecular Biology

Osteogenic potential of the growth factors and bioactive molecules in bone regeneration

Banafsheh Safari et al.

Summary: Bone tissue engineering aims to create bio-inspired systems with a coordinated combination of cells, scaffolds, and bioactive factors to repair damaged bone tissue. Bioactive factors such as cytokines, growth factors, peptides, and hormonal signals play a significant role in stimulating osteogenic differentiation and proliferation of cells.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2021)

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Article Engineering, Biomedical

Construction of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue

Jiani Gu et al.

Summary: Vascularization and bone regeneration are closely related processes during bone reconstruction. By combining 3D printing technology with phase separation and sacrificial template methods, a nanofibrous scaffold with interconnected perfusable microchannel networks was constructed to study the effects of microchannel structure on angiogenesis and osteogenesis.

BIOACTIVE MATERIALS (2021)

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Article Biochemistry & Molecular Biology

RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss

Yan Hu et al.

Summary: RANKL is essential for osteoclast formation and bone remodeling, with bone marrow adipose lineage cells being identified as a crucial cellular source for RANKL production. Conditional deletion of RANKL from these cells leads to an increase in cancellous bone mass in mice by reducing trabecular osteoclast formation and bone resorption, providing potential targets for preventing pathological bone loss.

EMBO REPORTS (2021)

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Article Cell Biology

Leptin Induced TLR4 Expression via the JAK2-STAT3 Pathway in Obesity-Related Osteoarthritis

Mengqi Jiang et al.

Summary: The study indicates that leptin may be an initiating factor in obesity-related osteoarthritis, regulating TLR4 through the JAK2-STAT3-CD14 pathway. Additionally, SOCS3 as a negative feedback inhibitor of leptin signaling presents a potential therapeutic prospect for obesity-related OA. The findings provide new evidence for the key role of leptin in mediating obesity-related OA and its underlying mechanisms.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2021)

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Article Multidisciplinary Sciences

Stat3 loss in mesenchymal progenitors causes Job syndrome-like skeletal defects by reducing Wnt/β-catenin signaling

Prem Swaroop Yadav et al.

Summary: Job syndrome is a rare genetic disorder characterized by immune dysfunction and skeletal developmental abnormalities. Current treatment options are limited, but enhancing Wnt/β-catenin signaling could potentially reduce bone symptoms in patients with Job syndrome.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Pharmacology & Pharmacy

Angelicin Alleviates Post-Trauma Osteoarthritis Progression by Regulating Macrophage Polarization via STAT3 Signaling Pathway

Zhansong Tian et al.

Summary: Post-trauma osteoarthritis (PTOA) is a common joint disease characterized by cartilage degeneration, with inflammation playing a crucial role. Regulation of inflammatory cells differentiation could be a potential therapeutic strategy for alleviating the condition.

FRONTIERS IN PHARMACOLOGY (2021)

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Article Rheumatology

Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis

Paola Di Benedetto et al.

Summary: During rheumatoid arthritis (RA), the angiogenic processes associated with pannus formation may be a therapeutic target. This study investigated the inhibitory role of the JAK inhibitor tofacitinib on angiogenic mechanisms in RA, revealing its ability to inhibit both in vitro EC angiogenic processes and in vivo synovial vessel formation in a CIA model. These findings suggest that tofacitinib's therapeutic effect in RA may be linked to its anti-angiogenic activity.

ARTHRITIS RESEARCH & THERAPY (2021)

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Review Rheumatology

Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis

Wenhui Hu et al.

Summary: This article discusses the changes in subchondral bone during OA progression and potential strategies for treating OA, including restoring abnormal remodeling and blocking blood vessels, highlighting the relationship between the subchondral bone microenvironment and OA pain.

ANNALS OF THE RHEUMATIC DISEASES (2021)

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Review Cell & Tissue Engineering

Subchondral bone microenvironment in osteoarthritis and pain

Yan Hu et al.

Summary: Osteoarthritis is a joint disorder characterized by cartilage degeneration and pain, with increasing global incidence due to aging and obesity trends. Research on the role of subchondral bone in osteoarthritis initiation and progression is crucial for understanding and treating the disease.

BONE RESEARCH (2021)

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Article Geriatrics & Gerontology

MiR-151a-3p Promotes Postmenopausal Osteoporosis by Targeting SOCS5 and Activating JAK2/STAT3 Signaling

Yin Fu et al.

REJUVENATION RESEARCH (2020)

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Article Orthopedics

Apatinib ameliorates doxorubicin-induced migration and cancer stemness of osteosarcoma cells by inhibiting Sox2 via STAT3 signalling

Zhi C. Tian et al.

JOURNAL OF ORTHOPAEDIC TRANSLATION (2020)

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Article Orthopedics

Genistein inhibits angiogenesis developed during rheumatoid arthritis through the IL-6/JAK2/STAT3/VEGF signalling pathway

Wen-Xiang Cheng et al.

JOURNAL OF ORTHOPAEDIC TRANSLATION (2020)

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Article Cell Biology

Icariin prevents oestrogen deficiency-induced alveolar bone loss through promoting osteogenesis via STAT3

Hongyuan Xu et al.

CELL PROLIFERATION (2020)

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Article Rheumatology

Incidence trend of five common musculoskeletal disorders from 1990 to 2017 at the global, regional and national level: results from the global burden of disease study 2017

Ziyi Jin et al.

ANNALS OF THE RHEUMATIC DISEASES (2020)

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Editorial Material Geriatrics & Gerontology

Osteosarcopenia: epidemiology, diagnosis, and treatment-facts and numbers

Ben Kirk et al.

JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE (2020)

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Article Biotechnology & Applied Microbiology

M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3

Yuan Xiong et al.

JOURNAL OF NANOBIOTECHNOLOGY (2020)

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Review Pharmacology & Pharmacy

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

Uddalak Bharadwaj et al.

PHARMACOLOGICAL REVIEWS (2020)

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Article Cell Biology

Neobavaisoflavone inhibits osteoclastogenesis through blocking RANKL signalling-mediated TRAF6 and c-Src recruitment and NF-κB, MAPK and Akt pathways

Huiwen Chen et al.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2020)

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Review Cell Biology

Mechanisms of bone development and repair

Ankit Salhotra et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2020)

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Review Biochemistry & Molecular Biology

JAK/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration

Alexandra Damerau et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Medicine, General & Internal

Association between the metabolome and bone mineral density in a Chinese population

Zhendong Mei et al.

EBIOMEDICINE (2020)

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Article Pharmacology & Pharmacy

Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes

Feng Zhou et al.

ACTA PHARMACEUTICA SINICA B (2019)

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Article Biochemistry & Molecular Biology

STAT3 controls osteoclast differentiation and bone homeostasis by regulating NFATc1 transcription

Yiling Yang et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

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Article Biochemistry & Molecular Biology

Cellular hypoxia promotes osteogenic differentiation of mesenchymal stem cells and bone defect healing via STAT3 signaling

Xin Yu et al.

CELLULAR & MOLECULAR BIOLOGY LETTERS (2019)

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Review Medicine, Research & Experimental

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

Qi Chen et al.

THERANOSTICS (2019)

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Article Endocrinology & Metabolism

Stat3 in osteocytes mediates osteogenic response to loading

Kylie A. Corry et al.

BONE REPORTS (2019)

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Article Biochemistry & Molecular Biology

Poria cocos polysaccharide attenuates RANKL-induced osteoclastogenesis by suppressing NFATc1 activity and phosphorylation of ERK and STAT3

Dezhi Song et al.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2018)

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Article Immunology

Stattic inhibits RANKL-mediated osteoclastogenesis by suppressing activation of STAT3 and NF-κB pathways

Chang-hong Li et al.

INTERNATIONAL IMMUNOPHARMACOLOGY (2018)

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Review Oncology

Targeting the IL-6/JAK/STAT3 signalling axis in cancer

Daniel E. Johnson et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2018)

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Article Biochemistry & Molecular Biology

Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing

Xin Yu et al.

BIOLOGICAL CHEMISTRY (2018)

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Article Immunology

The Therapeutic Effect of STAT3 Signaling-Suppressed MSC on Pain and Articular Cartilage Damage in a Rat Model of Monosodium Iodoacetate-Induced Osteoarthritis

Seon-yeong Lee et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Article Cell & Tissue Engineering

RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation

Xiao Chen et al.

BONE RESEARCH (2018)

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Article Rheumatology

Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis

Augustin Latourte et al.

ANNALS OF THE RHEUMATIC DISEASES (2017)

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Review Oncology

The JAK/STAT3 axis: A comprehensive drug target for solid malignancies

Jennifer Huynh et al.

SEMINARS IN CANCER BIOLOGY (2017)

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Review Biochemistry & Molecular Biology

Cell-specific paracrine actions of IL-6 family cytokines from bone, marrow and muscle that control bone formation and resorption

Natalie A. Sims

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY (2016)

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Article Cell Biology

EGFL7 Is Expressed in Bone Microenvironment and Promotes Angiogenesis via ERK, STAT3, and Integrin Signaling Cascades

Shek Man Chim et al.

JOURNAL OF CELLULAR PHYSIOLOGY (2015)

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Review Biochemistry & Molecular Biology

Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors

Kodappully Sivaraman Siveen et al.

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER (2014)

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Review Oncology

STATs in cancer inflammation and immunity: a leading role for STAT3

Hua Yu et al.

NATURE REVIEWS CANCER (2009)

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Article Cell Biology

Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NF kappa B

Jinbo Yang et al.

GENES & DEVELOPMENT (2007)

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Article Biochemistry & Molecular Biology

Stattic: A small-molecule inhibitor of STAT3 activation and dimerization

Jochen Schust et al.

CHEMISTRY & BIOLOGY (2006)

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Article Immunology

The STAT3 isoforms and have unique and specific functions

D Maritano et al.

NATURE IMMUNOLOGY (2004)

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Article Endocrinology & Metabolism

Growth hormone attenuates the transcriptional activity of Runx2 by facilitating its physical association with Stat3β

PG Ziros et al.

JOURNAL OF BONE AND MINERAL RESEARCH (2004)

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Review Biochemistry & Molecular Biology

Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis

CM Silva

ONCOGENE (2004)

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Stat3 Signaling Pathway: A Future Therapeutic Target for Bone-Related Diseases

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