Biology subjects

Hongwei, O.

Publications and source records attributed to Hongwei, O..

8 recordsLinked to original sources

bioRxiv2025

Immunotherapy with Pro-regenerative Macrophages from Embryonic Stem Cells Ameliorate Osteoarthritis via TNFAIP3-Mediated Chondroprotection

Immune cell-based therapies for osteoarthritis (OA) remains underexplored. Macrophages coordinate tissue repair, yet their functional heterogeneity and therapeutic applicability, particularly for designed stem cell-derived populations with tailored reparative properties are not fully delineated. Inspired by embryonic skeletal development as a paradigm of scarless regeneration, we identified a pro-regenerative macrophage population through a single-cell RNA atlas of developing skeletal tissues. We subsequently established a mechanically dynamic induction approach to efficiently generate pro-regenerative macrophages from human embryonic stem cells (hESCs), mimicking this developmental phenotype. In vitro, these macrophages mitigate cartilage degradation in OA explants and suppress pro-inflammatory, catabolic signaling in chondrocytes. Injection into murine OA joints robustly attenuates disease progression, reduces extracellular matrix breakdown, and resolves synovial inflammation, representing the first demonstration of immune cell-based therapy for OA. Mechanistically, these macrophages orchestrate chondroprotection not through broad immunosuppression, but by activating a TNFAIP3-dependent signaling hub that restrains inflammatory and catabolic responses in chondrocytes. This TNFAIP3 activation precisely reversed the OA-associated gene signature, suppressing catabolic mediators while enhancing reparative factors, thereby restoring the anabolic-catabolic balance. Our findings uncover a developmental blueprint for engineering pro-regenerative macrophages from stem cells and establish a pioneering targeted immune cell therapy that engages an intrinsic chondroprotective program, offering a transformative and translationally relevant strategy for OA treatment.

immunology↗

bioRxiv2024

Bio-macromolecular assembly machine for human limb lengthening

Growth plate (GP) is the critical cartilaginous structure for longitudinal bone growth. Herein, employing high-resolution analytical techniques, we explore the intricate mechanisms that govern the polarized mineralization patterns within GP. The GP-epiphysis interface displays a sharp transition in tissue modulus, acting as a "protective shell" for the underlying GP, whereas the GP-metaphysis interface exhibits a gradual modulus increase, enabling efficient load redistribution to metaphysis. The unique mechanical environments at these two interfaces contribute to polarized CaP mineralization patterns, which are regulated by a complex protein-based molecular machinery. The mineralization inhibitors SPP1 and AHSG enriched at the GP-epiphysis interface could act as a line of defence against mineralization. When these two proteins coexisted with the mineralization-promoting ENPP1 and ALPL at the GP-metaphysis interface, a sequential event of precise nucleation and programmable assembly of CaP minerals occur, forming "mineralization waves" to guide bone elongation. By replicating such specific macromolecular environment at GP-metaphysis interface, a hypertable amorphous calcium phosphate (ACP) phase is well-retained in vitro, demonstrating the possibility for precise and gentle control of ACP-hydroxyapatite (HAp) transformation under physiological conditions. Our study defines a novel concept of "mineralization waves" that govern the velocity and amplitude of GP-guided mineralization process.

bioengineering↗

bioRxiv2023

Distinct Microstructural Heterogeneities Underpin Specific Micromechanical Properties in Human ACL Femoral and Tibial Entheses

The anterior cruciate ligament (ACL) is anchored to the femur and tibia by a specialized interface tissue called the enthesis, which transfers forces in multiple directions and magnitudes without accruing fatigue damage during loading cycles over a lifetime. However, the precise structural and mechanical characteristics of the ACL femoral enthesis (FE) and tibial enthesis (TE) and their intricate interplay are unknown. In this study, we identified two ultrathin-graded mineralization regions in the FE ([~]21 m) and TE ([~]14 m), both of which exhibited distinct biomolecular compositions and mineral assembly patterns. FE interface exhibited progressively maturing hydroxyapatites (HAps), whereas minerals at the TE interface region changed from an amorphous phase (ACP) to HAps with increasing crystallinity. The LC-MS/MS results revealed that MGP protein uniquely enriched at the TE interface may be favorable for stabilizing ACP, while CLEC11A enriched at the FE interface could facilitate osteogenesis of the interface. The finite element analysis results indicated that the FE model was more resistant to shearing, while the TE model facilitated tensile resistance. It suggested that the great discrepancy in biomolecular expression and the corresponding mineral assembling heterogeneities together contributed to the superior mechanical properties of both the FE and TE models. These findings provide new perspectives regarding the management of ACL injury and the development of high-performance interface materials.

bioengineering↗

bioRxiv2023

Biomaterial based implants caused remote liver fatty deposition through activated blood-derived Kupffer cells

Understanding the foreign-body response (FBR) of biomaterials is a prerequisite for the prediction of its clinical application, and the present assessments mainly rely on in vitro cell culture and in situ histopathology. However, remote organs responses after biomaterials implantation is unclear. Here, by leveraging body-wide-transcriptomics data, we performed in-depth systems analysis of biomaterials - remote organs crosstalk after abdominal implantation of polypropylene and silk fibroin using a rodent model, demonstrating local implantation caused remote organs responses dominated by acute-phase responses, immune system responses and lipid metabolism disorders. Of note, liver function was specially disturbed, defined as hepatic lipid deposition. Combining flow cytometry analyses and liver monocyte recruitment inhibition experiments, we proved that blood derived monocyte-derived Kupffer cells in the liver underlying the mechanism of abnormal lipid deposition induced by local biomaterials implantation. Moreover, from the perspective of temporality, the remote organs responses and liver lipid deposition of silk fibroin group faded away with biomaterial degradation and restored to normal at end, which highlighted its superiority of degradability. These findings were further indirectly evidenced by human blood biochemical examination from 141 clinical cases of hernia repair using silk fibroin mesh and polypropylene mesh. In conclusion, this study provided knowledge of biomaterials-body interactions. It is of great important for future development of biomaterial devices for clinical application. One Sentence SummaryAbdominal local biomaterials implantation induces remote organ fatty deposition through activated blood-derived Kupffer cells.

pharmacology and toxicology↗

bioRxiv2022

Scale Bar of Aging Trajectories for Screening Personal Rejuvenation Treatments

Although aging is an increasingly severe healthy, economic, and social global problem, it is far from well-modeling aging due to the aging processs complexity. To promote the aging modeling, here we did the quantitative measurement based on aging blood transcriptome. Specifically, the aging blood transcriptome landscape was constructed through ensemble modeling in a cohort of 505 people, and 1138 age-related genes were identified. To assess the aging rate in the linear dimension of aging, we constructed a simplified linear aging clock, which distinguished fast-aging and slow-aging populations and showed the differences in the composition of immune cells. Meanwhile, the non-linear dimension of aging revealed the transcriptome fluctuations with a crest around the age of 40 and showed that this crest came earlier and was more vigorous in the fast-aging population. Moreover, the aging clock was applied to evaluate the rejuvenation effect of molecules in vitro, such as Nicotinamide Mononucleotide (NMN) and Metformin. In sum, this study developed a de novo aging clock to evaluate agedependent precise medicine by revealing its fluctuation nature based on comprehensively mining the aging blood transcriptome, promoting the development of personal aging monitoring and anti-aging therapies.

bioengineering↗

bioRxiv2021

High Resolution Nanostructure with Two-stages of Exponential Energy Dissipation at the Ultrathin Osteochondral Interface Tissue of Human Knee Joint

Cartilage adheres to subchondral bone via a specific osteochondral interface tissue where forces are transferred from soft cartilage to hard bone without fatigue damage over a lifetime of load cycles. However, the fine structure and mechanical properties of osteochondral interface tissue remain unclear. Here, we identified an ultrathin [~]20-30 m calcified region with two-layered micro-nano structures of osteochondral interface tissue in human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to the force transmission which was verified by finite element simulations. The nanoscale heterogeneity of hydroxyapatite, along with enrichment of elastic-responsive protein-titin which is usually present in muscle, endowed the osteochondral tissue with excellent energy dissipation and fatigue resistance properties. Our results provide potential design for high-performance interface materials for osteochondral interface regeneration and functional coatings.

bioengineering↗

bioRxiv2021

The shifting of dominating roles between structural cells and immune cells are key regulators of human adipose tissues aging

Adipose tissue is a highly dynamic organ with complex cellular composition. Aging induces adipose tissue function decline and relocation of peripheral adipose tissue to abdominal compartment, which often associated with inflammation and metabolic disorders. Here we performed single-cell RNA sequencing to comprehensively and unbiasedly deconvolve how subcutaneous adipose tissue (SAT) responses to aging. We collected >25,000 stromal vascular cells from abdominal and gluteofemoral SAT of young and old donors. Analyses of transcription signatures and cell networks uncovered impaired adipogenesis and extracellular matrix synthesis capacity of APC, altered metabolic phenotype of immune cells and shifted tissue-dominating cells that can be used to predict adipose tissue aging. We also reported aging-associated distinct transcriptional program between gluteofemoral SAT and abdominal SAT. Our work thus reveals unanticipated cellular, immunological, metabolic and site-specific aspects of human adipose tissues aging process, providing valuable resource for better understanding of aging-associated adipose tissue dysfunction.

pathology↗

bioRxiv2018

Diagnosis of Osteoarthritis Subtypes with Blood Biomarkers

ObjectiveTo identity osteoarthritis(OA) subtypes with gene expression of peripheral blood mononuclear cells.\n\nMethodsGene expression data (GSE48556) of Genetics osteoARthritis and Progression (GARP) study was downloaded from Gene Expression Omnibus. Principal component analysis and unsupervised clustering were analyzed to identify subtypes of OA and compare major KEGG pathways and cell type enrichment using GSEA and xCell. Classification of subtypes were explored by the utilization of support vector machine.\n\nResultsUnsupervised clustering identified two distinct OA subtypes: Group A comprised of 60 patients (56.6%) and Group B had 46 patients (43.3%). A classifier including nine genes and CD4+ T cell and Regulatory T cell flow cytometry could accurately distinguish patients from each group (area under the curve of 0.99 with gene expression). Group A is typical degenerative OA with glycosaminoglycan biosynthesis and apoptosis. Group B is related to Graft versus host disease and antigen processing and presentation, which indicated OA has a new type of \"Antigen processing and presentation\" similarly as that of RA.\n\nConclusionOA can be clearly classified into two distinguished subtypes with blood transcriptome, which have important significance on the development of precise OA therapeutics.

bioinformatics↗