Intra-articular drug delivery systems (DDS) are emerging as promising therapies for osteoarthritis (OA), yet their efficacy in spontaneous clinical cases remains largely untested. This uncontrolled, descriptive pilot study was designed to provide a proof of concept for the feasibility, safety, and preliminary clinical effects of intra-articular administration in sport horses with naturally occurring OA. The study involved a peptide-functionalized nanogel composed of chitosan and hyaluronic acid, delivering endothelin type A (BQ-123) and bradykinin B1 (R-954) receptor antagonists, which have previously demonstrated anti-inflammatory and chondroprotective properties in preclinical models. Eight client-owned sport horses with moderate OA of the metacarpophalangeal (MCPJ) or distal interphalangeal joint (DIPJ) received a single intra-articular injection of 2.4 mL nanogel and were followed for 12 months. No major adverse events were observed. Two horses developed mild, transient joint swelling that resolved within three days. Seven of eight horses showed improvement in lameness scores by week 12, although complete resolution on hard ground circles was observed in only two horses. All horses were sound on soft ground and returned to competition, with a median time of 128 days post-treatment. Six horses remained in active competition at one year without additional intervention. Four horses (50

Adolescent Idiopathic Scoliosis (AIS) is increasingly recognized as a multisystem disorder arising from the interplay between genetic susceptibility, metabolic dysregulation, and impaired mechanobiological signaling. Recent genomic studies highlight defects in ciliary genes, implicating disrupted ciliary structure and signaling in altered spinal growth. Concurrently, metabolic disturbances including pubertal hormones, oxidative stress, and altered IGF-1 activity may exacerbate these genetic vulnerabilities by influencing bone remodeling and extracellular matrix properties. Epigenetic regulators such as microRNAs and endocrine factors such as melatonin further integrate metabolic cues with gene expression programs relevant to skeletal development. Together, these converging pathways disrupt primary cilia-dependent mechanotransduction, leading to asymmetric vertebral growth during puberty. This integrated framework positions AIS as a systemic condition and highlights new opportunities for biomarker discovery and better understanding of AIS pathogenesis.

Objectives The objective of this study was to evaluate the impact of vitamin D (1,25VitD3) and orthodontic tooth movement (OTM) on alveolar bone, tooth movement type, and root structure. Design Sprague Dawley rats (n=32) were divided into four groups (n=8 per group): control gavage (CG), experimental gavage (EG), control injection (CI), and experimental injection (EI). OTM was induced using a NiTi spring. Micro-CT scans were performed at 5 time points: T0 (before 1,25VitD3 administration), T1 (OTM initiation), T2 (OTM completion), T3 (7 days post-OTM), T4 (30 days post-OTM) to measure alveolar bone height and tooth tipping. Root resorption was evaluated histologically. Results A significant decrease in buccal alveolar height was observed during and after OTM for 1,25VitD3 groups. Lingual alveolar bone decreased throughout the whole experiment for CI and EI, while it decreased only during OTM for EG. A significant increase in mesial tipping was observed between T0 and T2 for all groups. Root resorption was significantly higher for the OTM side than the control side for all groups (p<0.05). Conclusions Alveolar bone height decreased with OTM across all dental surfaces, with 1,25VitD3 enhancing this reduction at the buccal and lingual sites. The OTM also lead to significant mesial tipping and root resorption, which were not affected by 1,25VitD3.

Adolescent idiopathic scoliosis (AIS) is a multifactorial spinal deformity with poorly understood molecular mechanisms. This study investigates the role of the centrosomal protein POC5 in AIS pathogenesis using in vitro cellular systems and in vivo vertebrate models. POC5 mutations were found to disrupt centrosomal localization, impair ciliogenesis, alter cell-cycle progression, and reduce osteogenic differentiation. Functional analyses in zebrafish and mouse models revealed spinal deformities, retinal abnormalities, and multisystem defects consistent with ciliopathy-related phenotypes. These findings support a model in which POC5-dependent dysfunction contributes to AIS through impaired mechano-transduction and altered skeletal development.

Lubricin is a component of synovial fluid that contributes to minimizing friction by forming a hydrated boundary layer. However, injuries and diseases such as osteoarthritis may cause a deficiency in natural lubricin in the joints. Therefore, synthetic polymers are being examined as lubricin alternatives. Herein, well-defined poly(oligo (ethylene glycol) methyl ether methacrylate) POEGMA300-based bottlebrushes were obtained via atom transfer radical polymerization and successfully crosslinked with nanoparticles to form nanoparticle-bottlebrush polymer mixtures capable of carrying active substances. Analysis of morphology by atomic force microscopy revealed that both bottlebrushes and nanoparticle-bottlebrush polymer mixtures self-assembled on the mica surface into networks mimicking human lubricin. Lubrication properties were investigated by the surface force apparatus, considering the chemical composition of bottlebrushes and showed a reduction of the friction coefficient from 25 % to 60 % in comparison with phosphate buffered saline. Obtained structures showed no cytotoxicity and are promising materials for further studies.

Purpose:Meniscus injuries are common, but failed repairs remain an issue. The aim of this study was to demonstrate, in an in vivo rat model, the ability of growth differentiation factor 5 (GDF5) to improve meniscal tear healing. Methods:Eight Lewis rats (four females and four males) underwent radial tear of the medial meniscus on the right knee. There were two post-operative treatments: the GDF5 group (n = 4) received 0.1 mg/mL of GDF5, and the saline group (n = 4) a saline injection. The eight left knees were the control without surgery. Sacrifice was six weeks post-operatively. The GDF5 and saline groups were compared according to histology and meniscus healing score (MHS) in different zones: red-red (R-R), red-white (R-W) and white-white (W-W). Results:In the R-R zone, the median [interquartile range, IQR] MHS was 2.5 [2-3] in the GDF5 group and 2 [1.25-2] in the saline group (p = 0.200), and in the W-R zone it was 2 [2-2.75] for GDF5 and 1 [1-1.75] for saline (p = 0.047). There was no difference in the W-W zone (median MHS under one; p = 0.686). Regardless of groups, median [IQR] MHS in R-R (2 [2-2.75]) and R-W zones (2 [1-2]) were significantly higher (p < 0.001) than in the W-W zone (0 [0-1]). MHS intraclass correlation coefficient inter-observer was 0.88 and intra-observer was 0.90. Conclusions:GDF5 increases meniscal healing, especially in the R-W zone, although the W-W zone remains challenging. GFD5 is a promising factor for improving meniscus healing. The small sample size and absence of biomechanical evaluation are limitations that warrant caution when interpreting these findings. Further studies with larger sample sizes in larger animal models, combined with meniscal repair, are required to confirm these preliminary results. Study Design:Animal laboratory study. Level of Evidence:Level V, animal study.

Osteoarthritis (OA) is a widespread cause of physical disability and chronic pain, yet it lacks a pharmacological cure due to the difficulty of delivering drugs to avascular cartilage. We recently developed peptide-grafted nanogels for intra-articular injection that were well tolerated in vivo in healthy equine joints. Hence, this study reports the pharmaceutical aspects of this drug delivery system, which is based on biopolymeric nanohydrogels (nanogels, NG) for the localized, sustained delivery of two peptide antagonists of endothelin-1 (ETA) and bradykinin (BKB1), namely BQ123 and R954. Chitosan and hyaluronic acid were first functionalized with BQ123 and R954, respectively (CH-BQ123 and HA-R954), and subsequently used to synthesize nanogels via ionic gelation (NG BQ123 and NG R954). Peptide-conjugated NG were characterized for stability, peptide release in human synovial fluid, cytocompatibility, and biological efficacy in vitro in human chondrocytes. NG BQ123 and NG R954 showed slow, sustained release in synovial fluid for up to three months. Both were biocompatible with human chondrocytes and rapidly internalized by the cells. Notably, in vitro therapeutic effects were observed after only seven days of treatment, attributed to the slow peptide release reducing nitric oxide (NO) and Cyclooxygenase-2 expression. This study demonstrates a nanogel platform enabling localized, sustained peptide delivery, supporting the potential therapeutic use of NG BQ123 and NG R954 in OA treatment.

Osteoarthritis is a leading cause of pain and retirement in athletic horses. Hydro-expansive functionalized nanogels, acting as Drug Delivery Systems, constitute one of the current therapeutic prospects. These nanogels have the potential to combine mechanical benefits through polymers with the biological effect of prolonged release of bioactive molecules. The purpose of this double-blinded randomized tolerance study versus negative control was to evaluate the response of healthy joints to a single injection of the expected efficient dose (further referred to as the trial dose) and overdose of nanogels composed of chitosan and hyaluronic acid and featuring a type A endothelin receptor antagonist and a type B1 bradykinin receptor antagonist. The metacarpophalangeal joints of 8 healthy horses were randomly injected with 2.4 mL of functionalized nanogels and 2.4 mL of saline as control on the contralateral limb. Injections were repeated twice at one-week intervals, followed by injection of a triple dose of nanogel on week four. Clinical, ultrasonographic and synovial fluid cellular and biochemical follow-ups were performed up to three months following the first injection. No change in general clinical parameters, lameness or sensitivity to passive flexion of the fetlocks was noted. Mild to moderate synovitis was noted on the day following injection in the treated group, with a significant difference (p < 0.05) compared to the control group. It spontaneously resolved on day 3 following the injections and did not increase with repeated injections. Similar effects were noted after injection of the triple dose but lasted for a week. Synovial fluid markers of inflammation also showed a transient significant increase in the treated group one week after each injection, but no differences were detected at the end of the study. Injections of the expected therapeutic dose of functionalized nanogel in healthy joints induced a mild transient inflammatory response in the joint. Three injections of the trial dose at one-week intervals and injection of thrice the trial dose induce a mildly greater inflammation without harmful effects on joints. Functionalized nanogels are well tolerated prospects for the treatment of osteoarthritis in horses. Their beneficial effects on arthritic joints have yet to be evaluated to determine their therapeutic potential.

This systematic review, registered with Prospero, aims to identify an optimal animal model for meniscus repair research, moving from ex vivo experimentation to in vivo studies. Data sources included PubMed, Medline, all Evidence-Based Medicine Reviews, Web of Science, and Embase searched in March 2023. Studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Extracted data including animal model, type of experiment, type of tear, surgical techniques, and measured outcomes, were recorded, reviewed, and analyzed by four independent reviewers. The SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) Rob tool was used for critical appraisal and risk of bias assessment. Out of 11,719 studies, 72 manuscripts were included for data extraction and analysis; 41 ex vivo extra-articular studies, 20 ex vivo intra-articular studies, and only 11 in vivo studies. Six animal models were employed: porcine, bovine, lapine, caprine, canine, and ovine. Longitudinal lesions were the most frequently studied tear pattern and sutures the most common repair technique. Studied outcomes focused mainly on biomechanical assessments and gross observations. This systematic review can guide researchers in their choice of animal model for meniscus repair research; it highlighted the strengths of the porcine, caprine, and bovine models for ex vivo cadaveric studies, while the porcine and caprine models were found to be more suited to in vivo studies due to their similarities with human anatomy. Research teams should familiarize themselves with the advantages and disadvantages of various animal models before initiating protocols to improve standardization in the field.

Meniscal repair should be the gold standard. However, the meniscus is poorly vascularized and even an excellent meniscus repair may not heal. Therefore, numerous studies and systematic reviews have been carried out on platelet-rich plasma (PRP), mesenchymal stem cells (MSCs) and fibrin clots for meniscal augmentation, but the results remain controversial. This systematic review aimed to identify other emerging strategies for meniscal repair augmentation and to assess whether there are different avenues to explore in this field. A systematic literature review was conducted in August 2022. PubMed, Ovid MEDLINE(R) all, Ovid All EBM Reviews, Ovid Embase and ISI Web of Science databases were searched. In Vivo animal and human studies concerning the biological augmentation of meniscal lesions by factors other than PRP, MSCs or fibrin clots were included. Cartilage-only studies, previous systematic reviews and expert opinions were excluded. All data were analyzed by two independent reviewers. Of 8965 studies only nineteen studies covering 12 different factors met the inclusion criteria. Eight studies investigated the use of growth factors for meniscal biologic augmentation, such as vascular endothelial growth factor or bone morphogenic protein 7. Five studies reported on cell therapy and six studies focused on other factors such as hyaluronic acid, simvastatin or atelocollagen. Most studies (n = 18) were performed on animal models with gross observation and histological evaluation as outcomes. Polymerase chain reaction and immunohistochemistry were also common. Biomechanical testing was the object of only two studies. Although several augmentation strategies have been attempted, none has yielded conclusive results, testifying to a lack of understanding with regard to meniscal healing. More research is needed to better understand the pathways that regulate meniscus repair and how to act positively on them. Systematic review of case–control and animal laboratory studies.

Bottlebrush polymers (BB) have emerged as compelling candidates for biosystems to face tribological challenges, including friction and wear. This study provides a comprehensive assessment of an engineered triblock BB polymer's affinity, cell toxicity, lubrication, and wear protection in both in vitro and in vivo settings, focusing on applications for conditions like osteoarthritis and dry eye syndrome. Results show that the designed polymer rapidly adheres to various surfaces (e.g., cartilage, eye, and contact lens), forming a robust, biocompatible layer for surface lubrication and protection. The tribological performance and biocompatibility are further enhanced in the presence of hyaluronic acid (HA) both in vitro and in vivo. The exceptional lubrication performance and favorable interaction with HA position the synthesized triblock polymer as a promising candidate for innovative treatments addressing deficiencies in bio-lubricant systems.

Biocompatible bottlebrush polymer that could be used for combination therapy with synergistic effect in osteoarthritis treatment is presented within this work.

The burden of osteoarthritis (OA), one of the major causes of functional disabilities in humans and animals, continues to increase worldwide while no disease-modifying OA drugs (DMOADs) that either slow down or reverse disease progression have been made available. Here, we provide a brief overview of recent advances in: designing new OA drug delivery approaches, focusing on lubrication-based biomaterials and drug delivery systems, such as hydrogels, liposomes, dendrimers, micro- and nanoparticles; using either large (horse) or small (zebrafish) relevant animal models to evaluate new therapeutic strategies; and OA in vitro modeling, focusing on 3D (organoid) models of cartilage regarding the Replace, Reduce and Refine (3R) principle of animal experimentation.

Thymus atlanticus (Lamiaceae) is a plant endemic to the Mediterranean basin that is found in significant quantities in the arid regions of Morocco. Thymus atlanticus is used in traditional medicine to treat infectious and non-infectious diseases. It is also used for the isolation of essential oils and for the seasoning of many dishes in the Mediterranean diet. The major constituents of Thymus atlanticus are saponins, flavonoids, tannins, alkaloids, various simple and hydroxycinnamic phenolic compounds, and terpene compounds. Several of these compounds act on signaling pathways of oxidative stress, inflammation, and blood sugar, which are parameters often dysregulated during aging. Due to its physiochemical characteristics and biological activities, Thymus atlanticus could be used for the prevention and/or treatment of age-related diseases. These different aspects are treated in the present review, and we focused on phytochemistry and major age-related diseases: dyslipidemia, cardiovascular diseases, and type 2 diabetes.

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spinal deformity. The incidence of AIS in females is 8.4 times higher than in males. Several hypotheses on the role of estrogen have been postulated for the progression of AIS. Recently, Centriolar protein gene POC5 (POC5) was identified as a causative gene of AIS. POC5 is a centriolar protein that is important for cell cycle progression and centriole elongation. However, the hormonal regulation of POC5 remains to be determined. Here, we identify POC5 as an estrogen-responsive gene under the regulation of estrogen receptor ERα in normal osteoblasts (NOBs) and other ERα-positive cells. Using promoter activity, gene, and protein expression assays, we found that the POC5 gene was upregulated by the treatment of osteoblasts with estradiol (E2) through direct genomic signaling. We observed different effects of E2 in NOBs and mutant POC5A429V AIS osteoblasts. Using promoter assays, we identified an estrogen response element (ERE) in the proximal promoter of POC5, which conferred estrogen responsiveness through ERα. The recruitment of ERα to the ERE of the POC5 promoter was also potentiated by estrogen. Collectively, these findings suggest that estrogen is an etiological factor in scoliosis through the deregulation of POC5.

There are more than 900 genetic syndromes associated with oral manifestations. These syndromes can have serious health implications, and left undiagnosed, can hamper treatment and prognosis later in life. About 6.67% of the population will develop a rare disease during their lifetime, some of which are difficult to diagnose. The establishment of a data and tissue bank of rare diseases with oral manifestations in Quebec will help medical professionals identify the genes involved, will improve knowledge on the rare genetic diseases, and will also lead to improved patient management. It will also allow samples and information sharing with other clinicians and investigators. As an example of a condition requiring additional research, dental ankylosis is a condition in which the tooth's cementum fuses to the surrounding alveolar bone. This can be secondary to traumatic injury but is often idiopathic, and the genes involved in the idiopathic cases, if any, are poorly known. To date, patients with both identified and unidentified genetic etiology for their dental anomalies were recruited through dental and genetics clinics for the study. They underwent sequencing of selected genes or exome sequencing depending on the manifestation. We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS. Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases.