Search Results (1,251)

Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the dual roles of inflammatory and mechanical signaling in OA pathogenesis, focusing on crucial pathways such as NF-kB, JAK/STAT, and MAPK in inflammation, as well as Wnt/β-catenin, Integrin-FAK, and Hippo-YAP/TAZ in mechanotransduction. The interplay between these pathways highlights a vicious cycle wherein mechanical stress exacerbates inflammation, and inflammation weakens cartilage, increasing its vulnerability to mechanical damage. Additionally, we discuss emerging therapeutic strategies targeting these pathways, including inhibitors of cartilage-degrading enzymes, anti-inflammatory biologics, cell-based regenerative approaches, and non-pharmacological mechanical interventions. By dissecting the molecular mechanisms underlying OA, this review aims to provide insights into novel interventions that address both inflammatory and mechanical components of the disease, paving the way for precision medicine in OA management. Full article

Background/Objectives: Malnutrition is an imbalance of nutrients required for growth, development, and organ function. Its impact on bone development is known, but its effects on cartilage remain unclear. This study aimed to evaluate the femoral cartilage thickness in children with primary malnutrition. Methods: In this cross-sectional observational study, 83 children with primary malnutrition and 62 age- and sex-matched healthy controls were included. Patients with primary malnutrition were classified as mild, moderate and severe. Femoral cartilage thickness measurements of all children were taken by ultrasound from the femoral lateral condyle, femoral medial condyle and intercondylar area for both knees with the patient in a supine position with the knees flexed 90 degrees. Results: The right lateral, right medial, left lateral, and left medial femoral cartilages were significantly thicker in patients with malnutrition compared to those without malnutrition (p = 0.002, 0.004, <0.001, and 0.001, respectively). A significant negative correlation was found between age, weight Z-score, and height Z-score and triceps skinfold thickness. Conclusions: Distal femoral cartilage thickness is significantly greater in children with primary malnutrition. This demonstrates the effect of nutritional factors on cartilage tissue and suggests that children with chronic malnutrition are at risk for both knee joint problems and short stature later in life. Full article

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (Oryzias latipes), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages. TPhP impaired vertebral ossification, causing shortened centra and reduced cartilage in the caudal complex, alongside disrupted distribution of osteoblast-lineage cells. Key osteogenic genes were significantly downregulated at 14 days post fertilization, and transcriptomic analysis revealed altered mitochondrial pathways linked to skeletal disorders. Functionally, TPhP-exposed larvae showed reduced caudal fin regeneration and decreased metabolic rate and oxygen consumption, consistent with mitochondrial dysfunction. These findings indicate that TPhP disrupts bone development and metabolism by affecting osteoblast differentiation and mitochondrial regulation, highlighting the value of small fish models for studying environmental toxicants and bone metabolic disease risk. Full article

According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial for musculoskeletal tissue regeneration. This is due to their high water content (70–99%), ECM-like structure, injectability, and controllable degradation rates. Recent preclinical studies indicate that they can enhance regeneration by modulating the release of bioactive compounds, growth factors, and stem cells. Composite hydrogels that combine natural and synthetic polymers, like chitosan and collagen, have compressive moduli that are advantageous for tendon–bone healing. Some of these hydrogels can even hold up to 0.8 MPa of tensile strength. In osteoarthritis models, functionalized systems such as microspheres responsive to matrix metalloproteinase-13 have demonstrated disease modulation and targeted drug delivery, while intelligent in situ hydrogels have exhibited a 43% increase in neovascularization and a 50% enhancement in myotube production. Hydrogel-based therapies have been shown to restore contractile force by as much as 80%, increase myofiber density by 65%, and boost ALP activity in bone defects by 2.1 times in volumetric muscle loss (VML) models. Adding TGF-β3 or MSCs to hydrogel systems improved GAG content by about 60%, collagen II expression by 35–50%, and O’Driscoll scores by 35–50% in cartilage regeneration. Full article

Xylosyltransferase-I (XT-I) plays a crucial role in skeletal development and cartilage integrity. An XT-I deficiency is linked to severe bone disorders, such as Desbuquois dysplasia type 2. While animal models have provided insights into XT-I’s role during skeletal development, its specific effects on adult bone homeostasis, particularly in human mesenchymal stem cell (hMSC) differentiation, remain unclear. This study investigates how XT-I deficiency impacts the differentiation of hMSCs into chondrocytes, osteoblasts, and adipocytes—key processes in bone formation and repair. The aim of this study was to elucidate for the first time the molecular mechanisms by which XT-I deficiency leads to impaired bone homeostasis. Using CRISPR-Cas9-mediated gene editing, we generated XYLT1 knockdown (KD) hMSCs to assess their differentiation potential. Our findings revealed significant disruption in the chondrogenic differentiation in KD hMSCs, characterized by the altered expression of regulatory factors and extracellular matrix components, suggesting premature chondrocyte hypertrophy. Despite the presence of perilipin-coated lipid droplets in the adipogenic pathway, the overall leptin mRNA and protein expression was reduced in KD hMSCs, indicating a compromised lipid metabolism. Conversely, osteogenic differentiation was largely unaffected, with KD and wild-type hMSCs exhibiting comparable mineralization processes, indicating that critical aspects of osteogenesis were preserved despite the XYLT1 deficiency. In summary, these results underscore XT-I’s pivotal role in regulating differentiation pathways within the bone marrow niche, influencing cellular functions critical for skeletal health. A deeper insight into bone biology may pave the way for the development of innovative therapeutic approaches to improve bone health and treat skeletal disorders. Full article

Obesity, characterized by excessive or abnormal accumulation of body fat, is associated with a range of metabolic and inflammatory diseases, including osteoarthritis (OA). In obese individuals, adipose tissue expansion—via adipocyte hypertrophy or hyperplasia—is accompanied by altered secretion of adipokines such as leptin and adiponectin, which play significant roles in immune modulation, metabolism, and skeletal homeostasis. Leptin, acting through the hypothalamus, regulates the sympathetic nervous system and modulates hormonal axes, influencing bone metabolism and cartilage integrity. Elevated leptin concentrations in the synovial fluid, and the presence of its receptors on cartilage surfaces, suggest its direct role in cartilage degradation and OA progression. Conversely, adiponectin exerts anti-inflammatory effects, modulates osteoblast and macrophage activity, and appears to have a protective function in joint metabolism. These findings underscore the complex interplay between the adipose tissue, adipokines, and the osteochondral unit, highlighting the importance of their balance in maintaining joint health. Full article

Pedicle screw fixation is a critical technique for stabilizing lumbar fractures in canines, yet the biomechanical implications of insertion angles remain underexplored. This study aims to identify optimal screw trajectories by analyzing stress distribution and deformation patterns in beagle lumbar segments (L6-L7) using finite element analysis (FEA). A 3D finite element model was reconstructed from CT scans of a healthy beagle, incorporating cortical/cancellous bone, intervertebral disks, and cartilage. Pedicle screws (2.4 mm diameter, 22 mm length) were virtually implanted at angles ranging from 45° to 65°. A 10 N vertical load simulated standing conditions. Equivalent stress and total deformation were evaluated under static loading. The equivalent stress occurred at screw–rod junctions, with maxima at 50° (11.73 MPa) and minima at 58° (3.25 MPa). Total deformation ranged from 0.0033 to 0.0064 mm, with the highest at 55° and the lowest at 54°. The 58° insertion angle demonstrated optimal biomechanical stability with minimal stress concentration, with 56–60° as a biomechanically favorable range for pedicle screw fixation in canine lumbar fractures, balancing stress distribution and deformation control. Future studies should validate these findings in multi-level models and clinical settings. Full article

Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment. Full article

Introduction: The scapholunate interosseus ligament (SLIL) is critical for wrist stability, with injuries causing carpal instability and potential scapholunate advanced collapse (SLAC). This technical note presents a novel ligament-sparing surgical technique for treating SLIL tears ranging from grade 2 to 4 of the Garcia-Elias classification. Materials and Methods: A retrospective study was performed on ten patients treated with this novel technique. The technique involves a dorsal approach to the wrist through a 5–7 cm incision ulnar to Lister’s tubercle. After exposing the scapholunate joint, reduction is performed using Kirschner wires (K-wires) as joysticks, followed by stabilisation with three K-wires through the scapholunate, scapho-capitate, and radio-lunate joints. Two 2.3 mm suture anchors with double sutures are placed where the reduction K-wires were removed. One pair of sutures connects the anchors and any remaining SLIL tissue, while the second pair create a shoelace-like capsulodesis. Post-operative care includes staged K-wire removal at one and two months, with progressive rehabilitation before returning to weight-bearing activities at six months. Results: All patients improved in pain and function. The technique addresses SLIL injuries by restoring both coronal alignment through ligament repair and sagittal alignment via dorsal capsulodesis. The use of suture anchors and direct repair preserves the native tissue while reinforcing the dorsal capsule–scapholunate septum complex, avoiding the need for tendon grafts or extensive bone tunnelling. Conclusions: This ligament-sparing technique offers several advantages, including absence of donor site morbidity, minimal damage to carpal cartilage and vascularity, and preservation of surgical options should revision be necessary. The procedure effectively addresses both components of scapholunate instability while maintaining a relatively straightforward surgical approach. Full article

With the intensification of global aging, the incidence of age-related diseases (including cardiovascular, neurodegenerative, and musculoskeletal disorders) has been on the rise, and cellular senescence is identified as the core driving mechanism. Cellular senescence is characterized by irreversible cell cycle arrest, which is caused by telomere shortening, imbalance in DNA damage repair, and mitochondrial dysfunction, accompanied by the activation of the senescence-associated secretory phenotype (SASP). In this situation, proinflammatory factors and matrix-degrading enzymes can be released, thereby disrupting tissue homeostasis. This disruption of tissue homeostasis induced by cellular senescence manifests as characteristic pathogenic mechanisms in distinct disease contexts. In cardiovascular diseases, senescence of cardiomyocytes and endothelial cells can exacerbate cardiac remodeling. In neurodegenerative diseases, senescence of glial cells can lead to neuroinflammation, while in musculoskeletal diseases, it can result in the degradation of cartilage matrix and imbalance of bone homeostasis. This senescence-mediated dysregulation across diverse organ systems has spurred the development of intervention strategies. Interventional strategies include regular exercise, caloric restriction, senolytic drugs (such as the combination of dasatinib and quercetin), and senomorph therapies. However, the tissue-specific regulatory mechanisms of cellular senescence, in vivo monitoring, and safety-related clinical translational research still require in-depth investigation. This review summarizes the progress in pathological mechanisms and interventions, providing theoretical support for precision medicine targeting senescence, which is of great significance for addressing health challenges associated with aging. Full article

Tissue engineering is a growing field with multidisciplinary players in cell biology, engineering, and medicine, aiming to maintain, restore, or enhance functions of tissues and organs. The extracellular matrix (ECM) plays fundamental roles in tissue development, maintenance, and repair, providing not only structural support, but also critical biochemical and biomechanical cues that regulate cell behavior and signaling. Although its specific composition varies across different tissue types and developmental stages, matrix molecules influence various cell functional properties in every tissue. Given the importance of ECM in morphogenesis, tissue homeostasis, and regeneration, ECM-based bioscaffolds, developed through tissue engineering approaches, have emerged as pivotal tools for recreating the native cellular microenvironment. The aim of this study is to present the main categories of these scaffolds (i.e., natural, synthetic, and hybrid), major fabrication techniques (i.e., tissue decellularization and multidimensional bioprinting), while highlighting the advantages and disadvantages of each category, focusing on biological activity and mechanical performance. Scaffold properties, such as mechanical strength, elasticity, biocompatibility, and biodegradability are essential to their function and integration into host tissues. Applications of ECM-based bioscaffolds span a range of engineering and regenerative strategies, including cartilage, bone, cardiac tissue engineering, and skin wound healing. Despite promising advances, challenges remain in standardization, scalability, and immune response modulation, with future directions directed towards improving ECM-mimetic platforms. Full article

Thermosensitive hydrogels undergo reversible sol-gel phase transitions in response to changes in temperature. Owing to their excellent biocompatibility, mild reaction conditions, and controllable gelation properties, these hydrogels represent a promising class of biomaterials suitable for minimally invasive treatment systems in diverse biomedical applications. This review systematically summarizes the gelation mechanisms of thermosensitive hydrogels and optimization strategies to enhance their performance for broader application requirements. In particular, we highlight recent advances in injectable thermosensitive hydrogels as a carrier within stem cells, bioactive substances, and drug delivery for treating various tissue defects and diseases involving bone, cartilage, and other tissues. Furthermore, we propose challenges and directions for the future development of thermosensitive hydrogels. These insights provide new ideas for researchers to explore novel thermosensitive hydrogels for tissue repair and disease treatment. Full article

Rheumatoid arthritis (RA) is one of the most representative autoimmune diseases. The peculiarity of this disease is synovial inflammation, which results in joint destruction and often disability. Although there are still several pathogenetic mechanisms to be clarified, lately, most studies have highlighted the involvement of mitochondria in the onset and progression of the disease. Mitochondrial functions are connected to many metabolic processes and the delivery of proinflammatory mediators. Mitochondria play a crucial role in the physiopathology of RA, contributing to chronic inflammation, cartilage and bone injury and chronic autoimmune response. Mitochondrial activity influences many aspects of the disease that will be discussed in terms of their correlation with the onset and persistence of RA, starting from mitochondrial dynamics up to bone homeostasis, passing through DAMPs and affecting immune cell functionality. Recent therapeutic approaches aim to improve mitochondrial function, reduce oxidative stress, modulate mitochondria-mediated inflammation and restore energy metabolism homeostasis. Full article

Background/Objectives: Hypertension is a major contributor to cardiovascular diseases and is often intensified by psychological stress, which can also affect bone metabolism. Although both conditions independently compromise bone health, their combined impact—particularly under acute and chronic stress—remains unclear. This pilot study aimed to assess the effects of such stressors on bone structure in spontaneously hypertensive rats (SHRs). Methods: Forty male rats, both normotensive and SHRs, were randomly assigned to control, acute stress, or chronic stress groups. Acute stress involves a single 2 h physical restraint. Chronic stress was induced over 10 days using alternating stressors: agitation, forced swimming, physical restraint, cold exposure, and water deprivation. Tibial bones were analyzed by microcomputed tomography (micro-CT), and histology was performed using Hematoxylin and Eosin and Masson’s Trichrome stains. Results: Micro-CT showed increased trabecular bone volume in normotensive rats under chronic stress, whereas SHRs displayed impaired remodeling under both stress types. Histological analysis revealed preserved connective tissue overall but evident changes in growth plate structure among stressed rats. SHRs exhibited exacerbated trabecular formation and cartilage abnormalities, including necrotic zones. Conclusions: Both acute and chronic stress, especially in the context of hypertension, negatively affect bone remodeling and maturation. Despite the absence of overt inflammation, structural bone changes were evident, indicating potential long-term risks. These findings highlight the importance of further studies on stress–hypertension interactions in bone health as well as the exploration of therapeutic approaches to mitigate skeletal damage under such conditions. Full article