Biology subjects

Bian, F.

Publications and source records attributed to Bian, F..

7 recordsLinked to original sources

bioRxiv2026

Distinct Biological and Biomechanical Features in TMJ and Knee Cartilages

The temporomandibular joint (TMJ) and the knee joint are two of the most frequently used joints in the body, with the mandibular condylar cartilage (MCC) and the articular cartilage (AC) covering the joint bone surfaces, respectively. Compromised MCC functions lead to various temporomandibular disorders (TMD), including TMJ osteoarthritis (TMJ OA); however, the mechanisms governing MCC homeostasis and its biomechanical properties are still poorly understood. In this study, we comprehensively compared the biological and biomechanical features of the MCC and AC in mice. Histological analysis on P1, P21, 3-month, and 10-month mice revealed the most drastic structural differences between MCC and AC at occlusion establishment (P21), with MCC found to be more susceptible to age-associated cartilage degeneration. Immunostaining revealed differentially distributed cartilage extracellular matrix components in MCC and AC, including collagen type I, II, and X, and highly enriched expression of several key transcriptional factors at the posterior region of the MCC, including sex determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2), and scleraxis (SCX). The posterior MCC also houses a group of long-lasting, slow-proliferative cells, as evidenced by the BrdU/EdU incorporation assay, suggesting the presence of a potential stem/progenitor cell niche at the posterior TMJ. Unbiased nanoindentation analysis revealed distinct biomechanical features between these joint cartilages. MCC exhibits a significantly lower elastic modulus (EIT) than AC, with the highest EIT observed at the anterior TMJ, which is oppositely associated with the fibrous layer thickness, but positively correlated with the ratio of the collagen type X-positive matrix in the cartilaginous layer. Altogether, this study provides a basic understanding of the biological and biomechanical features of the cartilaginous tissues in two important joints, which may facilitate our understanding of the physiology in the TMJ and knee joint, and support the applications of mouse models to study TMJ dysfunctions.

developmental biology↗

bioRxiv2025

GPX4 Promotes Optic Nerve Regeneration and RGC Neuroprotection

Preventing retinal ganglion cells (RGCs)s soma and axon degeneration and promoting optic nerve (ON) regeneration holds great promise for effective glaucoma treatment. To explore potential neural repair strategies, we focused on glutathione peroxidase 4 (GPX4), a key regulator of lipid peroxidation. GPX4 is upregulated in surviving RGCs after acute ON crush or chronic ocular hypertension insult, and also in regenerating RGCs. AAV-mediated RGC-specific overexpression of GPX4 promotes significant ON regeneration and RGC survival, along with visual functional preservation, demonstrating the detrimental role of lipid peroxidation in glaucoma and the therapeutic potential of modulating lipid peroxidation through GPX4 in optic neuropathies.

neuroscience↗

bioRxiv2025

SOX2-VSX2 Co-Occupancy Shapes Retinal Neurogenesis Through Dynamic Chromatin Regulation

Retinal neurogenesis is mediated by the coordinated activities of a complex gene regulatory network (GRN) of transcription factors (TFs) in multipotent retinal progenitor cells (RPCs). How this GRN mechanistically guides neural competence remains poorly understood. In this study, we present integrated transcriptional, genetic, and genomic analyses to uncover the regulatory mechanisms of SOX2, a key factor in establishing neural identity in RPCs. We show that SOX2 is preferentially enriched in the RPC-specific enhancer landscape associated with essential regulators of retinogenesis. Disruption of SOX2 expression impairs retinogenesis, marked by a selective loss of enhancer activity near genes essential for RPC proliferation and lineage specification. We identified the RPC transcription factor VSX2 as a binding partner for SOX2, and together, SOX2 and VSX2 co-target a core, retina-specific chromatin repertoire characterized by enhanced TF binding and robust chromatin accessibility. This cooperative binding establishes a shared SOX2-VSX2 transcriptional code that promotes the expression of critical regulators of neurogenesis while repressing the acquisition of alternative lineage cell fate. Our data illuminate fundamental biological insights on how transcription factors act in concert to drive chromatin-based genetic programs underlying retinal neural identity.

developmental biology↗

bioRxiv2024

Inactivation of a non-canonical gp130 signaling arm attenuates chronic systemic inflammation and multimorbidity induced by a high-fat diet.

Interleukin-6 (IL-6) is a major pro-inflammatory cytokine for which the levels in plasma demonstrate a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes, primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer a unique opportunity for therapeutic interventions. Recently, we discovered that a non-canonical signaling pathway downstream of tyrosine (Y) 814 within the intracellular domain of gp130, the IL-6 co-receptor, is responsible for the recruitment and activation of SRC family of kinases (SFK). Mice with constitutive genetic inactivation of gp130 Y814 (F814 mice) show accelerated resolution of inflammatory response and superior regenerative outcomes in skin wound healing and posttraumatic models of osteoarthritis. The current study was designed to explore if selective genetic or pharmacological inhibition of the non-canonical gp130-Y814/SFK signaling reduces systemic chronic inflammation and multimorbidity in a high-fat diet (HFD)-induced model of accelerated aging. F814 mice showed significantly reduced inflammatory response to HFD in adipose and liver tissue, with significantly reduced levels of systemic inflammation compared to wild type mice. F814 mice were also protected from HFD-induced bone loss and cartilage degeneration. Pharmacological inhibition of gp130-Y814/SFK in mice on HFD mirrored the effects observed in F814 mice on HFD; furthermore, this pharmacological treatment also demonstrated a marked increase in physical activity levels and protective effects against inflammation-associated suppression of neurogenesis in the brain tissue compared to the control group. These findings suggest that selective inhibition of SFK signaling downstream of gp130 receptor represents a promising strategy to alleviate systemic chronic inflammation. Increased degenerative changes and tissue senescence are inevitable in obese and aged organisms, but we demonstrated that the systemic response and inflammation-associated multi-morbidity can be therapeutically mitigated.

cell biology↗

bioRxiv2024

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN{Delta}C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C- terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

neuroscience↗

bioRxiv2023

Spatial Transcriptomics Reveals the Requirement of ADGRG6 in Maintaining Chondrocyte Homeostasis in Mouse Growth Plates

The growth plate is essential for maintaining skeletal growth; however, the mechanisms governing postnatal growth plate homeostasis are poorly understood. Here we show that ADGRG6/GPR126, a cartilage-enriched G protein-coupled receptor (GPCR), is dispensable for embryonic limb development but is required for postnatal growth plate homeostasis. Adgrg6 ablation in osteochondral progenitor cells or postnatal chondrocytes leads to reduced cellularity and impaired maintenance of the resting zone in the growth plate, coupled with increased cell death and reduced cell proliferation. Adgrg6 mutant growth plates also exhibit disorganized extracellular matrix structures and dysregulated hypertrophic differentiation. Furthermore, using a novel spatial transcriptomics workflow that applies to FFPE tissue sections of mineralized mouse knee joints, we demonstrate that Adgrg6 ablation leads to reduced SOX9 expression, induced Indian hedgehog (IHH) signaling, and a precocious chondrogenic-to-osteogenic conversion of the growth plate chondrocytes that may be driven by increased POSTN/integrin receptor signaling. We further demonstrated that ADGRG6 regulates the proper formation of the resting zone growth plate by maintaining the PTHrP and SOX9-positive cell populations. Altogether, our findings elucidate the essential role of ADGRG6 in maintaining chondrocyte fate, survival, and homeostasis of the postnatal growth plates.

molecular biology↗

bioRxiv2022

Gli1+ mesenchymal progenitors contribute to multilineage differentiation in a mouse model of post-traumatic joint injury

Complex injury and open reconstructive surgeries of the knee often lead to joint dysfunction that may alter the normal biomechanics of the joint. Two major complications that often arise are excessive deposition of fibrotic tissue and acquired heterotopic endochondral ossification. Knee arthrofibrosis is a fibrotic joint disorder where aberrant buildup of scar tissue and adhesions develop around the joint. Heterotopic ossification is ectopic bone formation around the periarticular tissues. Even though arthrofibrosis and heterotopic ossification pose an immense clinical problem, limited studies focus on their cellular and molecular mechanisms. Effective cell-targeted therapeutics are needed, but the cellular origin of both knee disorders remains elusive. Moreover, all the current animal models of knee arthrofibrosis and stiffness are developed in rats and rabbits, limiting genetic experiments that would allow us to explore the contribution of specific cellular targets to these knee pathologies. Here, we present a novel mouse model of post-traumatic joint injury where surgically induced injury and hyperextension of the knee lead to excessive deposition of disorganized collagen in the meniscus, synovium, and joint capsule in addition to formation of extra-skeletal bone in muscle and soft tissues within the joint capsule. As a functional outcome, arthrofibrosis and heterotopic endochondral ossification coupled with a significant increase in total joint stiffness were observed. By employing this model and genetic lineage tracing, we also demonstrate that Gli1+ mesenchymal progenitors proliferate after joint injury and contribute to fibrotic cells in the synovium and ectopic osteoblasts within the joint capsule. These findings demonstrate that Gli1+ cells are a major cellular contributor to knee arthrofibrosis and heterotopic ossification that manifests after knee injury. Our data collectively shows that genetic manipulation of Gli1+ cells in mice may offer a platform for identification of novel therapeutic targets to prevent chronic knee joint dysfunction after chronic injury.

pathology↗