Search Results (2,091)

Collagen peptides have been widely studied for their beneficial effects on skin health; however, their potential role in hair growth remains insufficiently explored. This study aimed to investigate the effects of orally administered low-molecular-weight fish collagen peptide (SH-GT) on hair regrowth and its underlying mechanisms in a hair-removed C57BL/6J mouse model. Mice were administered SH-GT (100, 300, or 600 mg/kg body weight) or a positive control (Pansidil, 400 mg/kg) daily for 28 days. SH-GT significantly enhanced hair regrowth, as evidenced by the increased hair growth area. Histological analysis revealed increased dermal thickness and visible hair follicle structures in SH-GT-treated groups. At the molecular level, SH-GT upregulated proliferation-related proteins, including PCNA and Cyclin D1, and activated Wnt/β-catenin signaling. In addition, SH-GT enhanced PI3K/Akt/mTOR signaling, suggesting improved cellular growth and survival. Conversely, SH-GT suppressed hair growth inhibitory pathways by reducing BMP4 expression and decreasing Smad phosphorylation. Furthermore, SH-GT increased the mRNA expression of growth factors such as IGF-1, HGF, VEGF, EGF, and FGF7. In conclusion, SH-GT promotes hair regrowth by simultaneously activating proliferation-related signaling pathways and suppressing inhibitory mechanisms, thereby improving the dorsal skin microenvironment associated with hair regrowth. These findings suggest that SH-GT may serve as a promising functional ingredient for improving hair growth. Full article

Objective: This systematic review aimed to evaluate the effects of biomimetic surface engineering strategies applied to dental implants on osseointegration and peri-implant bone regeneration compared with conventional implant surfaces. Materials and Methods: A comprehensive literature search was conducted in the Web of Science, PubMed, and Scopus databases in accordance with the PRISMA guidelines, covering the period from January 2021 to January 2026. A total of 12 studies, including in vivo animal experiments and in vitro investigations, that met the inclusion criteria were analyzed. Risk of bias assessment was performed using the SYR-CLE tool and the ARRIVE guidelines. Results: Biomimetic strategies, including laser texturing, sulfonation, bioactive coatings, and growth factor/peptide functionalization (e.g., BMP-2, FGF-2, and PRF), significantly increased bone–implant contact (BIC), new bone volume (BV/TV), and biomechanical stability (pullout strength and reverse torque) compared to conventional surfaces. These surfaces enhance fixation under conditions of low bone density, such as osteoporosis, and improve infection resistance through antibacterial activity. In addition, these modifications enhance cellular adhesion, osteogenic differentiation, angiogenesis, and immune modulation. Conclusions: Current experimental evidence suggests that biomimetic implant surface engineering transforms dental implants from passive biomaterials into multifunctional bioactive interfaces capable of simultaneously regulating osteogenesis, immune response, angiogenesis, and antibacterial activity. Although promising outcomes have been demonstrated in preclinical studies, standardized long-term human clinical studies are still required to validate translational potential and long-term clinical efficacy. Full article

The transforming growth factor-beta (TGF-β) superfamily regulates diverse biological processes, including proliferation, differentiation, apoptosis, tissue remodeling, and reproductive signaling across metazoans. Here, we performed a genome-wide characterization of the TGF-β gene family in donkey (Equus asinus, ASM1607732v2) using comparative genomics and bioinformatics analyses, with horse (Equus caballus, EquCab3.0) as a reference to investigate evolutionary conservation and functional divergence. Genome assemblies and proteomes were retrieved from NCBI, and TGF-β genes were identified using BLASTp and HMMER searches (Pfam PF00019), followed by phylogenetic, conserved motif, synteny, Ka/Ks, mutation prediction, subcellular localization, and tissue-specific expression analyses. We identified 40 TGF-β genes in donkeys, exceeding the numbers reported in several mammals, suggesting possible lineage-specific expansion or differential gene retention within Equidae. Phylogenetic and motif analyses demonstrated strong evolutionary conservation across the two principal clades (TGF-β-like and BMP-like). Four segmental duplications were identified, with Ka/Ks ratios ranging from 0.28 to 0.43, indicating strong purifying selection on duplicated genes. Synteny analysis revealed extensive collinearity with the horse genome, supporting conserved equid genomic architecture. Comparative sequence analysis identified 160 amino acid variants, including 11 predicted deleterious mutations in key genes (GDF6, GDF9, GDF10, BMP15, and RGMA), suggesting potential functional divergence associated with reproductive and developmental pathways. Importantly, transcriptomic validation using publicly available donkey RNA-seq tissue expression data (NCBI BioProject: PRJNA1017964) revealed distinct tissue-specific expression patterns, with reproductive tissues (ovary and uterus) displaying enriched expression of TGF-β/BMP signaling components, particularly TGFBR1, TGFBR2, TGFB1, BMP2, BMP4, and BMP7, while canonical fecundity genes (GDF9 and BMP15) exhibited ovary-associated expression. This receptor-dominant signaling profile may have a coordinated TGF-β regulatory network underlying folliculogenesis, reproductive tissue remodeling, and fertility-related processes in donkeys. Subcellular localization predictions showed that most proteins (22/40) were extracellularly localized, consistent with conserved signaling functions. Together, this study provides the first integrated genomic and tissue-expression atlas of the donkey TGF-β superfamily, offering new insights into equid-specific evolutionary conservation, reproductive signaling, and functional divergence. Full article

Prolificacy and coat color are key economic traits influencing sheep production. This study evaluated a reduced panel of 48 SNPs previously associated with these traits and assessed its applicability to locally adapted Brazilian sheep breeds. A total of 1152 samples from 15 breeds, conserved in situ at conservation nuclei and ex situ in the Brazilian Animal Germplasm Bank, were genotyped. Allelic, genotypic, and haplotypic frequencies were estimated to compare genetic variability between in situ and ex situ populations. Additionally, linkage disequilibrium (LD) among SNPs within GDF9, a key gene associated with prolificacy, was evaluated across local breeds, revealing strong LD among specific markers. The results highlight the importance of the FecG^E (GDF9) variant for prolificacy in hair sheep, confirming the presence of mutant allele E in prolific breeds, such as Santa Inês and Morada Nova, and identifying, for the first time, a high frequency of such allele in the Brazilian Blackbelly, which provides new insights into the genetic basis of this prolific hair breed. Other prolificacy-related genes, BMP15 and BMPR1B, appear to have no functional role in locally adapted breeds, as initially hypothesized, considering genetic differences among European and tropical sheep. Allelic and genotypic variation in ASIP, MC1R, TYRP1, and MITF genes reflected differences between wool and hair sheep and between local and commercial breeds. Overall, the results indicate that the germplasm bank effectively preserves in situ diversity. In conclusion, the reduced SNP panel efficiently genotyped Brazilian sheep for prolificacy and coat color SNPs, confirming which markers are present and segregating in these breeds. However, its utility could be improved by removing markers of limited relevance in the targeted breeds. Full article

As a traditional element of Chinese medicine, Hippocampus erectus is well known for promoting adolescent growth, yet its active fractions and underlying molecular mechanisms remain unclear. In this study, the aqueous extract of H. erectus was subjected to in vitro simulated gastrointestinal digestion and ultrafiltration to separate three molecular weight fractions (<10 kDa, 10–30 kDa, >30 kDa). Their chemical profiles were characterized, and osteogenic activities were systematically evaluated using cell assays, a juvenile rat model, and integrated transcriptomics and data-independent acquisition (DIA) proteomics. Results revealed that chemical profiling showed the >30 kDa fraction was mainly composed of hemocyanin subunits, and the 10–30 kDa fraction was enriched in growth-related amino acids and steroid derivatives; functionally, the 10–30 kDa fraction promoted preosteoblast proliferation and early differentiation via enhanced alkaline phosphatase (ALP) activity, while the >30 kDa fraction dominated late osteoblast maturation and mineralization. Both fractions significantly increased rat body and bone length by expanding growth plate proliferative zones and elevating serum insulin-like growth factor-1 (IGF-1)/bone morphogenetic protein-2 (BMP-2) levels. Transcriptomic and proteomic analyses identified vascular endothelial growth factor (VEGF), Wingless-related integration site (Wnt), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and extracellular matrix (ECM)–receptor interaction as potential core regulatory pathways. Integrated multi-omics analysis further confirmed Frizzled-related protein B (Frzb) and AKT1 substrate 1 (Akt1s1) as candidate key regulatory targets enriched in the Wnt and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways. These findings elucidate the multi-fraction, multi-pathway mechanism of H. erectus in promoting skeletal development, providing scientific evidence for its traditional use and a theoretical basis for growth-promoting functional food development. Full article

Londin et al. discovered a novel group of miRNAs, referred to as LmiRNAs, whose properties had been studied little for unknown reasons. In this study, we examine fully complementary interactions between LmiRNAs and mRNAs of human genes. Using the MirTarget program, we identified a significant number of target genes showing unique interaction with LmiRNAs. Among the 3707 LmiRNAs, fully complementary binding sites (BSs) were found in the 5′UTR of 75 target genes, with their interactions exhibiting high free energy. Fully complementary LmiRNA binding sites were located within the CDS of 81 target genes, while only seven LmiRNAs were found to bind to the 3′UTR of target genes. The KIFC3, PHF15, RPL15, and SNX11 genes were found to encode both LmiRNA-5p and LmiRNA-3p, which actively bind to their respective mRNAs. While the mRNA of most genes was targeted by only a single LmiRNA, the BMP8B, FGFRL1, and SDC3 genes included mRNAs bound by the specific pair ID00121.5p and ID02992.5p. These results expand our understanding of LmiRNAs and support their potential as diagnostic and therapeutic agents for various diseases. Full article

Objective: Icariin (ICA) is an active small molecule extracted from Epimedium, possessing therapeutic potential for inflammatory bone destruction. Small extracellular vesicles (MEVs) derived from bovine milk are safe and efficient drug delivery carriers. We aimed to explore the potential of ICA-loaded bovine milk EVs (ICA-MEVs) to repair inflammatory bone defects in an inflammatory microenvironment and investigated the underlying molecular mechanism, providing new ideas for the treatment of inflammatory bone defects. Methods: We fabricated icariin (ICA)-loaded milk-derived extracellular vesicles (ICA-MEVs) embedded in GelMA hydrogel and systematically evaluated the in vivo repairing efficacy against lipopolysaccharide (LPS)-induced inflammatory calvarial bone defects via micro-CT, HE staining, Masson staining and immunohistochemistry. Subsequent in vitro cellular experiments were carried out to uncover the regulatory mechanism by which ICA-MEVs promotes LPS-inhibited osteoblast proliferation and osteogenic differentiation. Results: ICA-MEVs significantly promoted the repair of inflammatory bone defects, upregulated osteogenic factors such as BMP-2, OCN, and Runx-2, and reduced the levels of IL-1β and TNF-α. ICA-loaded MEVs facilitated the proliferation and osteogenic differentiation of MC3T3-E1 osteoblasts while alleviating cellular inflammatory activation. Mechanistically, ICA-MEVs promoted bone repair by elevating LIM1 expression. Elevated LIM1 bound to the endogenous HIF-1α promoter and triggered subsequent transcriptional activation of HIF-1α. Conclusions: Under inflammatory conditions, ICA-MEVs effectively promoted the proliferation and differentiation of MC3T3-E1 cells and inhibited the expression of inflammatory factors. Mechanistically, ICA-MEVs upregulated HIF-1α transcription and expression by potentiating the LIM1-mediated transcriptional activation of the HIF-1α promoter, thereby facilitating inflammatory bone repair. Although milk-derived EVs exhibited favorable safety profiles in this preclinical study, comprehensive detection of immunogenicity and long-term adverse reactions will be necessary in follow-up research to support clinical transformation. Full article

Objectives: Autologous bone grafting remains the gold standard for maxillofacial reconstruction but is limited by tissue scarcity and donor-site morbidity. Consequently, substitutes like bioactive glass (BG), beta-tricalcium phosphate (β-TCP), and deproteinized bovine bone (DBB) are widely used. However, comprehensive mechanistic comparisons among them remain scarce. Materials and Methods: We systematically evaluated these substitutes under standardized in vitro conditions to compare their physicochemical transformations, degradation profiles, biological performances, and underlying osteogenic molecular pathways. Results: In simulated body fluid, BG underwent rapid hydroxyapatite mineralization, whereas the highly porous DBB and dense β-TCP remained structurally inert. Degradation assays revealed BG exhibited the fastest mass loss and ion release, β-TCP showed intermediate degradation, and DBB maintained high in vitro structural stability. Biologically, all materials showed favorable cytocompatibility and comparable angiogenic potential. However, BG demonstrated significant antibacterial activity (E. coli, S. aureus) and a strong potential to enhance osteogenic differentiation, significantly upregulating the protein-level expression of RUNX2 and OCN, alongside the transcriptional upregulation of Bmp2, Runx2, and Ocn. Transcriptomic profiling and pharmacological validation suggest that the enhanced osteogenic performance of BG might be associated with specific regulatory pathways, supporting the hypothesis that the suppression of NF-κB-mediated inflammation and the activation of the ECM-Integrin-FAK mechanotransduction axis play potential roles. Conclusions: BG offers high bioactivity and notable potential to enhance osteogenic differentiation in vitro but degrades rapidly. DBB ensures structural durability without intrinsic osteoinductivity, and β-TCP provides a balanced, intermediate profile. These in vitro mechanistic insights provide a theoretical foundation for future in vivo evaluations and designing next-generation bone scaffolds. Full article

Organophosphate flame retardants (OPFRs) are widely used as flame-retardant additives in plastics, electronics, and building materials. However, growing evidence suggests these compounds may pose significant neurotoxic risks. This study evaluated phenotypic alterations, such as cell viability, reactive oxygen species generation, and acetylcholinesterase activity, induced by seven widely detected OPFRs in SH-SY5Y human neuroblastoma cells. Aromatic OPFRs such as triphenyl phosphate (TPhP), 2-ethylhexyldiphenyl phosphate (EHDPhP) and tricresyl phosphate (TCP) exhibited the strongest effects, including decreased cell viability, increased oxidative stress and AChE inhibition. Therefore, 3D brain organoid models were used to further explore the potential lipidomic alterations induced by aromatic OPFRs. Lipidomic analysis of brain organoids exposed to aromatic OPFRs (TPhP, EHDPhP and TCP) showed significant alterations across major lipid classes, especially glycerophospholipids, sphingolipids, and glycerolipids. The depletion of bis(monoacylglycerol)phosphate (BMP) species suggests perturbations in endolysosomal lipid homeostasis and membrane trafficking pathways. Increased levels of ether-linked lysophosphatidylcholine (LPC-O) species, together with altered phosphatidylethanolamine (PE) and phosphatidylserine (PS) species, indicate extensive membrane lipid remodeling and changes in cellular signaling. Furthermore, the accumulation of diacylglycerol (DG) and triacylglycerol (TG) species points to disturbances in lipid storage and metabolism. Overall, these findings indicate that aromatic OPFRs induce cytotoxicity, oxidative stress, and alteration of cholinergic function, and are associated with lipid dysregulation linked to neurotoxicity in brain organoids. Future research should explore chronic low-dose exposure and long-term neurological effects. Full article

Hepcidin, a 25-amino-acid peptide hormone produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis. By binding the cellular iron exporter ferroportin and inducing its internalization and lysosomal degradation, hepcidin restricts iron entry into plasma from enterocytes, macrophages, and hepatocytes. Its transcription is governed by an intricate molecular network that integrates iron status, erythropoietic demand, oxygen tension, and inflammation, with the BMP–HJV–ALK2/SMAD axis acting as the canonical activating pathway and erythroferrone (ERFE) and matriptase-2 (TMPRSS6) as physiological suppressors. Dysregulation of hepcidin underpins a wide spectrum of human diseases: insufficient hepcidin drives hereditary hemochromatosis and the iron overload of congenital and acquired ineffective erythropoiesis diseases and other ineffective erythropoiesis syndromes, whereas excessive or inappropriate hepcidin contributes to anemia of inflammation, anemia of chronic kidney disease, iron-restricted erythropoiesis in cancer, the iron-restrictive anemia of myelofibrosis, and pathogen-restrictive nutritional immunity. Within the myeloproliferative neoplasm spectrum, the divergent hepcidin patterns observed in polycythemia vera (suppressed) and myelofibrosis (inappropriately elevated through dual BMP/ACVR1/SMAD and IL-6/STAT3 hyperactivation) exemplify the clinical relevance of this axis and underpin two opposite pharmacologic strategies. Over the past decade, hepcidin pathway pharmacology has matured from proof-of-concept to regulatory milestones, shifting perspectives on several diseases and markedly improving clinical approaches. Full article

Maternal exposure to airborne particulate matter smaller than $2.5$ μm (${\mathrm{PM}}_{2.5}$) has been associated with adverse fetal outcomes, although its effects on intramembranous ossification remain poorly understood. This study evaluated the impact of gestational and pregestational exposure to wood-smoke-derived ${\mathrm{PM}}_{2.5}$ on fetal neurocranial ossification in Sprague–Dawley rats. Females were allocated to four exposure conditions combining filtered air (FA) and non-filtered air (NFA): FA/FA, FA/NFA, NFA/FA, and NFA/NFA. Fetuses were collected at gestational day 21 and analyzed using fetal morphometry, radiography, micro-computed tomography, whole-mount alizarin red skeletal staining, histology, and immunohistochemistry for HIF-1$\alpha$, COL-1, BMP-2, FGF-R1, and TGF-$\beta$. Continuous exposure (NFA/NFA) was associated with reduced fetal weight, shorter crown–rump length, impaired craniofacial mineralization, widened cranial sutural regions, and reduced mineral density, particularly in the occipital and interparietal bones. Histologically, exposed fetuses exhibited abundant osteoid, reduced osteocyte incorporation, and diffuse osteoblastic distribution, consistent with delayed osteogenic maturation. Immunohistochemistry showed increased HIF-1$\alpha$ immunoreactivity, altered TGF-$\beta$ regulation, and reduced COL-1 expression in continuously exposed fetuses, whereas BMP-2 and FGF-R1 showed no significant changes. These findings suggest that maternal exposure to wood-smoke-derived PM_2.5 is associated with delayed fetal neurocranial intramembranous ossification, particularly under continuous exposure. The observed immunohistochemical profile, elevated HIF-1$\alpha$, reduced COL-I, and altered TGF-$\beta$, is consistent with a hypoxia-associated imbalance between extracellular matrix deposition and mineral maturation; however, the underlying mechanistic pathway was not directly functionally tested and should be regarded as a biologically plausible inferential model requiring further experimental validation. Full article

Cleft lip with or without cleft palate (CL/P) is one of the most common congenital craniofacial anomalies worldwide and presents significant functional, esthetic, and psychosocial challenges. Despite advances in multidisciplinary care and surgical reconstruction, complications such as impaired wound healing, scar formation, and growth disturbances warrant the development of novel regenerative and surgical strategies, which heavily rely on animal models at the pre-clinical stage. For the current narrative review, the literature search was performed by combining cleft phenotype terms with modeling-approach terms in six databases and was supplemented by manual review of reference lists from full-text articles. The included articles were summarized based on cleft type and the methods for cleft induction (chemically induced, genetically engineered, and surgically created). Particularly, chemical teratogens such as retinoic acid, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), corticosteroids, and 6-aminonicotinamide have been widely used to induce cleft phenotypes and elucidate environmental influences on palatogenesis, whereas genetic models have clarified the roles of key molecules and signaling pathways, including Sonic hedgehog (SHH), bone morphogenetic protein (BMP), and transforming growth factor-β (TGF-β), in the development of lip and palate. Meanwhile, the surgical models have focused on the alveolar cleft in skeletally mature animals for evaluating novel grafting materials. By comparing the strengths and limitations of existing models, this review highlights opportunities for improving experimental design and translational relevance in future cleft research. Overall, despite a wide range of CL/P animal models available, few replicate clinically relevant defect anatomy and the postnatal craniofacial deformation observed in CL/P patients, underscoring the need for the development of new models. Full article

Osteoarthritis (OA) remains a challenging disease due to the increased rate of incidence in the older population and the lack of a disease-modifying drug. BMP signaling plays a crucial role in chondrogenic differentiation and in the stability of articular cartilage. However, because BMP-2 also induces chondrocyte hypertrophy, it is not a viable drug for OA treatment. In contrast, the Bmpr1a biomimetic peptide can repair articular cartilage without inducing chondrocyte hypertrophy in the OA mouse model and in chondrocytes derived from patients diagnosed with OA. Despite this benefit, the mechanism by which the peptide drives chondrogenesis remains elusive. To explore this, we use a phosphoproteomics approach to identify pathways differentially activated by CK2.1. Specifically, we identified differentially phosphorylated phosphosites by CK2.1. Based on these phosphosites that we identified, we propose a molecular mechanism by which CK2.1 activates chondrogenesis. Notably, we predict that the mitogen-activated protein kinase (MAPK) pathway is regulated by CK2.1 to induce proteoglycan synthesis in C3H10T1/2 cells. Full article

Hulunbuir short-tailed sheep (HSTS) and Hu sheep (HS) exhibit distinct tail phenotypes linked to ecological adaptation, with HSTS carrying a loss-of-function mutation (c.G334T) in the T gene while HS retain the wild-type allele. However, the cellular and molecular mechanisms underlying T-mediated tail development remain unclear. Here, we performed single-cell RNA sequencing on HSTS and HS embryos at embryonic days 16 and 19 (E16 and E19), complemented by cross-species validation using a CRISPR/Cas9 mouse model carrying the same mutation. We identified 12 cell types in E16 HSTS and E16 HS embryos, and 15 cell types in E19 HSTS and E19 HS embryos and found that the MDK_ITGA6+ITGB1 ligand–receptor pair consistently mediated core intercellular communication. The MDK_ITGA6+ITGB1 axis mediates intercellular communication critical for tail bud formation; BMP activation and FGF repression disrupt AER survival, leading to tail shortening. Developmental trajectories showed a shift from early progenitor states at E16 to terminal differentiation at E19. Crucially, HSTS embryos showed transcriptomic signatures consistent with premature AER regression. The T mutation showed transcriptomic signatures of increased BMP pathway activity and reduced FGF8 expression, which may disrupt AER survival and contribute to the short-tail phenotype. In the mouse model, mutant T expression was reduced, and expression dynamics of WNT5B and FGF8 were perturbed, corroborating the sheep findings; however, homozygous T mutation causes embryonic lethality in mice but not in sheep, indicating species-specific differences. This study provides single-cell transcriptomic evidence linking the T c.G334T mutation to premature AER regression in sheep, complemented by cross-species validation in a CRISPR/Cas9 mouse model, offering new insights into the cellular mechanisms of tail development and may provide a basis for future investigations into tail-related breeding markers, pending experimental validation. These changes are associated with AER maintenance and tail outgrowth. Full article

Segmental bone defects and age-related osteoarthritis (OA) are clinically challenging in terms of treatment. Although preclinical studies have demonstrated efficacy for bone defect healing and OA using ex vivo gene therapy or biomaterial sustained-release delivery, few such treatments have translated into clinical therapies due to safety concerns. Bone morphogenetic proteins belong to the transforming growth factor β (TGFβ) superfamily and are effective in bone and cartilage regeneration/repair. Among BMPs, BMP4 is not only effective in promoting bone and cartilage repair but also promotes stem cell renewal potential and exhibits anti-aging effects. Therefore, the aim of this study is to investigate whether human BMP4 mRNA encapsulated in lipid nanoparticles (hBMP4 mRNA/LNP) can promote bone and cartilage repair. In vitro data demonstrated that hBMP4 mRNA/LNP-treated human MSCs secreted BMP4 protein, as detected by ELISA, and enhanced osteogenic differentiation. In vivo results demonstrated that hBMP4 mRNA/LNP at a 50 µg dose promoted limited new bone formation only at 2 weeks after creation of defect in critical-sized calvarial bone defects in aged mice when delivered using fibrin sealant hydrogel, as revealed by micro-CT and histology. However, intra-articular injection (IA) of lower doses (2.5 and 5 µg) in aged mice knee joints prevented cartilage loss, as demonstrated by micro-CT; decreased OARSI histology scores; and improved cartilage-specific matrix COL2. hBMP4 mRNA/LNP at a 5 μg dose significantly increased SOX9⁺ cells per normalized cartilage area as well as the percentage of SOX9⁺ cells in the cartilage area. hBMP4 mRNA/LNP treatment showed a trend of pain alleviation and did not change serum hyaluronic acid levels. In conclusion, human BMP4 mRNA encapsulated in lipid nanoparticles improved cartilage repair and delayed cartilage degeneration in aged mice, while having a limited effect on bone healing, even at a higher dosage. These results suggest that hBMP4 mRNA encapsulated with lipid nanoparticles represents a promising treatment for age-related OA. Full article