Articular Joint Research Articles

A spike in circulating cytokines TNF-α and TGF-β alters barrier function between vascular and musculoskeletal tissues

Molecular transport between the circulatory and musculoskeletal systems regulates articular joint physiology in health and disease. Osteoarthritis (OA) is a degenerative joint disease linked to systemic and local inflammation. Inflammatory events involve cytokines, which are secreted by cells of the immune system and modulate molecular transport across tissue interfaces (referred to as tight junction [TJ] barrier function). In a previous study from our group, OA knee joint tissues were shown to exhibit size separation of different sized molecules delivered as a single bolus to the heart (Ngo et al. in Sci. Rep. 8:10254, 2018). Here, in a follow up study of parallel design, we test the hypothesis that two common cytokines, with multifaceted roles in the etiology of osteoarthritis as well as immune state in general, modulate the barrier function properties of joint tissue interfaces. Specifically, we probe the effect of an acute cytokine increase (spike) on molecular transport within tissues and across tissue interfaces of the circulatory and musculoskeletal systems. A single bolus of fluorescent-tagged 70 kDa dextran, was delivered intracardially, either alone, or with either the pro-inflammatory cytokine TNF-α or the anti-inflammatory cytokine TGF-β, to skeletally mature (11 to 13-month-old) guinea pigs (Dunkin-Hartley, a spontaneous OA animal model). After five minutes' circulation, whole knee joints were serial sectioned and fluorescent block face cryo-imaged at near-single-cell resolution. The 70 kDa fluorescent-tagged tracer is analogous in size to albumin, the most prevalent blood transporter protein, and quantification of tracer fluorescence intensity gave a measure of tracer concentration. Within five minutes, a spike (acute doubling) in circulating cytokines TNF-α or TGF-β significantly disrupted barrier function between the circulatory and musculoskeletal systems, with barrier function essentially abrogated in the TNF-α group. In the entire volume of the joint (including all tissue compartments and the bounding musculature), tracer concentration was significantly decreased in the TGF-β- and TNF-α- compared to the control-group. These studies implicate inflammatory cytokines as gatekeepers for molecular passage within and between tissue compartments of our joints and may open new means to delay the onset and mitigate the progression of degenerative joint diseases such as OA, using pharmaceutical and/or physical measures.

Evaluation of expanded peripheral blood derived CD34+ cells for the treatment of moderate knee osteoarthritis.

Knee osteoarthritis (OA) is a degenerative joint disease of the knee that results from the progressive loss of articular cartilage. It is most common in the elderly and affects millions of people worldwide, leading to a continuous increase in the number of total knee replacement surgeries. These surgeries improve the patient's physical mobility, but can lead to late infection, loosening of the prosthesis, and persistent pain. We would like to investigate if cell-based therapies can avoid or delay such surgeries in patients with moderate OA by injecting expanded autologous peripheral blood derived CD34+ cells (ProtheraCytes®) into the articular joint. In this study we evaluated the survival of ProtheraCytes® when exposed to synovial fluid and their performance in vitro with a model consisting of their co-culture with human OA chondrocytes in separate layers of Transwells and in vivo with a murine model of OA. Here we show that ProtheraCytes® maintain high viability (>95%) when exposed for up to 96 hours to synovial fluid from OA patients. Additionally, when co-cultured with OA chondrocytes, ProtheraCytes® can modulate the expression of some chondrogenic (collagen II and Sox9) and inflammatory/degrading (IL1β, TNF, and MMP-13) markers at gene or protein levels. Finally, ProtheraCytes® survive after injection into the knee of a collagenase-induced osteoarthritis mouse model, engrafting mainly in the synovial membrane, probably due to the fact that ProtheraCytes® express CD44, a receptor of hyaluronic acid, which is abundantly present in the synovial membrane. This report provides preliminary evidence of the therapeutic potential of CD34+ cells on OA chondrocytes in vitro and their survival after in vivo implantation in the knee of mice and merits further investigation in future preclinical studies in OA models.

Antibiotic Treatment Prior to Injury Abrogates the Detrimental Effects of LPS in STR/ort Mice Susceptible to Osteoarthritis Development.

Post traumatic osteoarthritis (PTOA) is a form of secondary osteoarthritis (OA) that develops in ~50% of cases of severe articular joint injuries and leads to chronic and progressive degradation of articular cartilage and other joint tissues. PTOA progression can be exacerbated by repeated injury and systemic inflammation. Few studies have examined approaches for blunting or slowing down PTOA progression with emphasis on systemic inflammation; most arthritis studies focused on the immune system have been in the context of rheumatoid arthritis. To examine how the gut microbiome affects systemic inflammation during PTOA development, we used a chronic antibiotic treatment regimen starting at weaning for 6 weeks before anterior cruciate ligament (ACL) rupture in STR/ort mice combined with lipopolysaccharide (LPS)-induced systemic inflammation. STR/ort mice develop spontaneous OA as well as a more severe PTOA phenotype than C57Bl/6J mice. By 6 weeks post injury, histological examination showed a more robust cartilage staining in the antibiotic-treated (AB) STR/ort mice than in the untreated STR/ort controls. Furthermore, we also examined the effects of AB treatment on systemic inflammation and found that the effects of LPS administration before injury are also blunted by AB treatment in STR/ort mice. The AB- or AB+LPS-treated STR/ort injured joints more closely resembled the C57Bl/6J VEH OA phenotypes than the vehicle- or LPS-treated STR/ort, suggesting that antibiotic treatment has the potential to slow disease progression and should be further explored therapeutically as prophylactic post injury. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Osteoarthritis genetic risk acting on the galactosyltransferase gene COLGALT2 has opposing functional effects in articulating joint tissues

BackgroundInvestigation of cartilage and chondrocytes has revealed that the osteoarthritis risk marked by the independent DNA variants rs11583641 and rs1046934 mediate their effects by decreasing the methylation status of CpG dinucleotides in enhancers and increasing the expression of shared target gene COLGALT2. We set out to investigate if these functional effects operate in a non-cartilaginous joint tissue.MethodsNucleic acids were extracted from the synovium of osteoarthritis patients. Samples were genotyped, and DNA methylation was quantified by pyrosequencing at CpGs within the COLGALT2 enhancers. CpGs were tested for enhancer effects using a synovial cell line and a reporter gene assay. DNA methylation was altered using epigenetic editing, with the impact on gene expression determined using quantitative polymerase chain reaction. In silico analysis complemented laboratory experiments.ResultsThe rs1046934 genotype did not associate with DNA methylation or COLGALT2 expression in the synovium, whereas the rs11583641 genotype did. Surprisingly, the effects for rs11583641 were opposite to those previously observed in cartilage. Epigenetic editing in synovial cells revealed that enhancer methylation is causally linked to COLGALT2 expression.ConclusionsThis is the first direct demonstration for osteoarthritis genetic risk of a functional link between DNA methylation and gene expression operating in opposite directions between articular joint tissues. It highlights pleiotropy in the action of osteoarthritis risk and provides a cautionary note in the application of future genetically based osteoarthritis therapies: an intervention that decreases the detrimental effect of a risk allele in one joint tissue may inadvertently increase its detrimental effect in another joint tissue.

Inflammation-Mediated Aberrant Glucose Metabolism in Subchondral Bone Induces Osteoarthritis.

Osteoarthritis (OA) is an entire joint disease with pathological alteration in both articular cartilage and subchondral bone. It has been recognized recently the association between metabolic syndrome and OA, particularly glucose metabolism in regulation of articular cartilage homeostasis and joint integrity. Whereas the role of glucose metabolism in subchondral bone sclerosis remains largely unknown during pathogenesis of OA. Consistent with common OA features, we observed subchondral bone sclerosis and abnormal bone remodeling in human OA joints and murine OA joints as reflected by hyperactive bone resorption and overall bone formation which was measured via dynamic histomorphometry. Osx-CreER;tdTomato mice also displayed the similar overall bone formation under injury-induced OA condition. Immunohistochemistry further revealed increased IL-1β expression in human and murine OA subchondral bone. Given the inflammatory environment in joints under OA condition, we treated MC3T3-E1 cell, a pre-osteoblast cell line, with IL-1β in this study and demonstrated that IL-1β treatment could stimulate the cell osteogenic differentiation and meanwhile upregulate glycolysis and oxidative phosphorylation in cell cultures. More importantly, intraperitoneal injection of 2-deoxy-D-glucose (2-DG) and oligomycin (OGM), respectively, suppressed the subchondral bone glycolysis and oxidative phosphorylation in mice. Consequently, 2-DG and OGM treatment attenuated abnormal osteoblast differentiation and protected against aberrant bone formation in subchondral bone and articular cartilage degradation in wildtype mice following with joint injury. Collectively, these data strongly suggest glycolysis and oxidative may serve as important therapeutic targets for OA treatment.

Promotion of Joint Degeneration and Chondrocyte Metabolic Dysfunction by Excessive Growth Hormone in Mice.

Many patients with acromegaly, a hormonal disorder with excessive growth hormone (GH) production, report pain in joints. We undertook this study to characterize the joint pathology of mice with overexpression of bovine GH (bGH) or a GH receptor antagonist (GHa) and to investigate the effect of GH on regulation of chondrocyte cellular metabolism. Knee joints from mice overexpressing bGH or GHa and wild-type (WT) control mice were examined using histology and micro-computed tomography for osteoarthritic (OA) pathologies. Additionally, cartilage from bGH mice was used for metabolomics analysis. Mouse primary chondrocytes from bGH and WT mice, with or without pegvisomant treatment, were used for quantitative polymerase chain reaction and Seahorse respirometry analyses. Both male and female bGH mice at ~13 months of age had increased knee joint degeneration, which was characterized by loss of cartilage structure, expansion of hypertrophic chondrocytes, synovitis, and subchondral plate thinning. The joint pathologies were also demonstrated by significantly higher Osteoarthritis Research Society International and Mankin scores in bGH mice compared to WT control mice. Metabolomics analysis revealed changes in a wide range of metabolic pathways in bGH mice, including beta-alanine metabolism, tryptophan metabolism, lysine degradation, and ascorbate and aldarate metabolism. Also, bGH chondrocytes up-regulated fatty acid oxidation and increased expression of Col10a. Joints of GHa mice were remarkably protected from developing age-associated joint degeneration, with smooth articular joint surface. This study showed that an excessive amount of GH promotes joint degeneration in mice, which was associated with chondrocyte metabolic dysfunction and hypertrophic changes, whereas antagonizing GH action through a GHa protects mice from OA development.

An Integrated View of Stressors as Causative Agents in OA Pathogenesis.

Cells in the body are exposed to dynamic external and internal environments, many of which cause cell damage. The cell's response to this damage, broadly called the stress response, is meant to promote survival and repair or remove damage. However, not all damage can be repaired, and sometimes, even worse, the stress response can overtax the system itself, further aggravating homeostasis and leading to its loss. Aging phenotypes are considered a manifestation of accumulated cellular damage and defective repair. This is particularly apparent in the primary cell type of the articular joint, the articular chondrocytes. Articular chondrocytes are constantly facing the challenge of stressors, including mechanical overloading, oxidation, DNA damage, proteostatic stress, and metabolic imbalance. The consequence of the accumulation of stress on articular chondrocytes is aberrant mitogenesis and differentiation, defective extracellular matrix production and turnover, cellular senescence, and cell death. The most severe form of stress-induced chondrocyte dysfunction in the joints is osteoarthritis (OA). Here, we summarize studies on the cellular effects of stressors on articular chondrocytes and demonstrate that the molecular effectors of the stress pathways connect to amplify articular joint dysfunction and OA development.

The synovial environment steers cartilage deterioration and regeneration

Osteoarthritis (OA) was recently defined as an epidemic, and the lack of effective treatment is highly correlated to the limited knowledge regarding the underlying pathophysiology. Failure to regenerate upon trauma is thought to be one of the underlying causes for degenerative diseases, including OA. To investigate why lesions within an OA environment fail to heal, a heterogeneous cell population was isolated from the synovial fluid (SF) of OA patients. The cells' ability to undergo processes required for functional tissue regeneration was evaluated in the presence or absence of autologous SF. The obtained mechanistic findings were then used for the development of an immunomodulatory cell treatment, aimed to restore the pro-regenerative environment. Intra-articular injection in a clinical compassionate use study showed that the treatment restored the articular cartilage and joint homeostasis of OA patients. These findings confirm the role of pro-regenerative immune cells and their targeted influence on progenitor cells for degenerative joint disease therapies.

Shapes of cervical articular process joints and association with histological evidence of osteochondrosis in Warmblood foals: A post-mortem study.

Osteochondrosis dissecans (OCD) of articular process joints (APJs) is involved in cervical vertebral compressive myelopathy (CVM). Biomechanical forces, important in development of OCD, depend on joint conformation. Oval and flat APJ surfaces are considered normal. To identify and grade gross shape variation of cervical and cranial thoracic APJ surfaces and determine association with histological evidence of osteochondrosis. Case series. Eight hundred and four cervical and cranial thoracic APJ surfaces of 30 foals were evaluated for shape(s) and grades, and were correlated with osteochondrosis. Three top view shapes (oval, pointed, elongated) and seven lateral view shapes (flat, convex, concave, stepped, bevelled, folded edge, raised edge) were regularly encountered. The oval top view shape was most common. Flat and bevelled were the most common lateral view shapes. General shape grade of caudal articular surfaces was significantly higher than of cranial surfaces. The combinations of an oval top view shape and the lateral view shapes folded edge, concave, or flat with additional raised edge and/or folded edge (flat +), were more likely to have OC than oval with convex, bevelled or flat lateral view shapes (normal vs. oval and folded, odds ratio [OR] 2.49 [95% confidence intervals (CIs) 1.13-5.67]; normal vs. oval and flat +, OR 2.77 [95% CI 1.15-6.85]; oval and convex vs. oval and folded, OR 3.20 [95% CI 1.35-8.20]; oval and convex vs. oval and flat +, OR 3.56 [95% CI 1.43-9.54]; oval and bevelled vs. oval and concave, OR 2.02 [95% CI 1.14-3.60]; oval and bevelled vs. oval and folded, OR 3.50 [95% CI 1.91-6.60]; oval and bevelled vs. oval and flat +, OR 3.90 [95% CI 2.00-7.70]). Most foals (21/30) were less than 1 month old. Lack of observer reliability scores for shape and shape grade. APJs shape might contribute to CVM by increased likelihood to have OC.

Interobserver agreement of lateral and oblique radiography and standing cone beam CT of the caudal cervical articular process joints of horses.

Caudal cervical articular process joint osteoarthritis (CAPJ OA) leads to career-altering clinical signs in the horse. Oblique radiographs and standing cone beam computed tomography (CBCT) facilitate the assessment of this area, however, the variability of interpretation of these images is currently unknown. This retrospective, secondary analysis, methods comparison study investigated interobserver agreement between clinicians and modality in grades of CAPJ OA on lateral and oblique radiographs and CBCT. We hypothesized that agreement between clinicians' grades of CAPJ OA would be lowest for oblique radiographs and highest for CBCT, and agreement between grades of CAPJ OA would be low for all pairs of modalities. Horses underwent lateral and oblique radiography and CBCT of the CAPJs of C5-C6 and C6-C7. Radiographs and CBCT images were graded retrospectively by four blinded clinicians using 3-point scales. Cohen's kappa analysis was used to evaluate interobserver agreement between grades of CAPJ OA, and agreement between grades of CAPJ OA between different modalities was explored using kappa-weighted analysis. Agreement between clinicians' grades of CAPJ OA was moderate for lateral radiographs (0.49), and fair for oblique radiographs (0.23) and CBCT (0.36). For all modalities, agreement was slight to fair between clinicians for CAPJs with grade 1 (normal, 0.21-0.32) or 2 (mild, 0.13-0.36) CAPJ OA, and moderate to substantial for grade 3 (moderate to severe, 0.45-0.77) CAPJ OA. Agreement between grades of CAPJ OA was fair for all pairs of modalities. This study provides important information regarding the inconsistency of interpretation of mild CAPJ OA on radiographs and CBCT amongst clinicians.

Marine-Inspired Approaches as a Smart Tool to Face Osteochondral Regeneration.

The degeneration of osteochondral tissue represents one of the major causes of disability in modern society and it is expected to fuel the demand for new solutions to repair and regenerate the damaged articular joints. In particular, osteoarthritis (OA) is the most common complication in articular diseases and a leading cause of chronic disability affecting a steady increasing number of people. The regeneration of osteochondral (OC) defects is one of the most challenging tasks in orthopedics since this anatomical region is composed of different tissues, characterized by antithetic features and functionalities, in tight connection to work together as a joint. The altered structural and mechanical joint environment impairs the natural tissue metabolism, thus making OC regeneration even more challenging. In this scenario, marine-derived ingredients elicit ever-increased interest for biomedical applications as a result of their outstanding mechanical and multiple biologic properties. The review highlights the possibility to exploit such unique features using a combination of bio-inspired synthesis process and 3D manufacturing technologies, relevant to generate compositionally and structurally graded hybrid constructs reproducing the smart architecture and biomechanical functions of natural OC regions.

Digits in a dish: An in vitro system to assess the molecular genetics of hand/foot development at single-cell resolution.

In vitro models allow for the study of developmental processes outside of the embryo. To gain access to the cells mediating digit and joint development, we identified a unique property of undifferentiated mesenchyme isolated from the distal early autopod to autonomously re-assemble forming multiple autopod structures including: digits, interdigital tissues, joints, muscles and tendons. Single-cell transcriptomic analysis of these developing structures revealed distinct cell clusters that express canonical markers of distal limb development including: Col2a1, Col10a1, and Sp7 (phalanx formation), Thbs2 and Col1a1 (perichondrium), Gdf5, Wnt5a, and Jun (joint interzone), Aldh1a2 and Msx1 (interdigital tissues), Myod1 (muscle progenitors), Prg4 (articular perichondrium/articular cartilage), and Scx and Tnmd (tenocytes/tendons). Analysis of the gene expression patterns for these signature genes indicates that developmental timing and tissue-specific localization were also recapitulated in a manner similar to the initiation and maturation of the developing murine autopod. Finally, the in vitro digit system also recapitulates congenital malformations associated with genetic mutations as in vitro cultures of Hoxa13 mutant mesenchyme produced defects present in Hoxa13 mutant autopods including digit fusions, reduced phalangeal segment numbers, and poor mesenchymal condensation. These findings demonstrate the robustness of the in vitro digit system to recapitulate digit and joint development. As an in vitro model of murine digit and joint development, this innovative system will provide access to the developing limb tissues facilitating studies to discern how digit and articular joint formation is initiated and how undifferentiated mesenchyme is patterned to establish individual digit morphologies. The in vitro digit system also provides a platform to rapidly evaluate treatments aimed at stimulating the repair or regeneration of mammalian digits impacted by congenital malformation, injury, or disease.

Laser Melt Infiltration of UHMWPE into the Binary Coatings of Strontium Apatite and Colloidal Silica

Medical-grade ultrahigh molecular weight polyethylene (UHMWPE) is the material of choice for sliding surfaces in various articular joint implants owing to its excellent biocompatibility and superior physical properties, such as an exceptionally low coefficient of friction and excellent durability. However, the bioinert nature of UHMWPE limits its extended use in rapidly advancing medical fronts. In this study, bioactive surface modifications of UHMWPE were addressed using a newly developed laser-melt infiltration technique. UHMWPE was coated with binary mixtures of strontium apatite and colloidal silica particles and irradiated using a 30 W CO2 laser to reach the maximum temperature of 150 ± 5 °C. UHMWPE melts infiltrated the porous matrices of the coatings by capillary force and formed surface-selective composite materials between them. Capillary rise heights were evaluated by observing the uplift of the substrate after the selective dissolution of the coating substances and were found to be much higher than the estimated values based on the Lucas–Washburn equation. This finding suggests that the melt viscosity of UHMWPE confined within the nanopores might be significantly lower than that measured at macroscopic scales. Both strontium and silicate ions are known osteo-inductive factors, and their concentrations eluted from the binary coatings were substantially higher than those found in the single coatings.

Quantitative morphometric analysis in tibiofemoral joint osteoarthritis imaging: A literature review

ObjectiveTo highlight published quantitative morphometric analysis (QMA) methods for assessing tibiofemoral joint osteoarthritis in magnetic resonance imaging and computed tomography and underline the need for open and interoperable protocols for quantitative image analysis. DesignA literature search on PubMed/MEDLINE and Web of Science of keywords relating to QMA in magnetic resonance imaging and computed tomography in the context of tibiofemoral osteoarthritis in the past 23 years (2000–2022). The search was based on, but not limited to: “quantitative morphometric analysis” or “quantitative image analysis” in combination with “osteoarthritis”, “articular cartilage”, “subchondral bone”, “tibiofemoral joint”, “joint”, “CT”, and “MRI”. The search found 73 relevant publications that were manually screened and sorted for QMA methods. A further search to extract key functions of the underlying algorithms was performed. ResultMRI is generally used for QMA of articular cartilage and joint contact area, while CT is generally used for QMA of subchondral bone and joint space width. Studies have shown that QMA algorithms can be adapted to new tissues and modalities. However, many methods are not easily accessible, and there is fragmentation of computational tools and platforms in the research field. ConclusionQMA is an active research area, and many techniques from one modality can be readily extended to another. Adoption of open-source practices can allow algorithms developed for other imaging modalities to be shared, making it possible to bridge the knowledge gap for structures and pathological features for which QMA has not yet been investigated and to increase research output overall.

Replication Study of Molded Micro-Textured Samples Made of Ultra-High Molecular Weight Polyethylene for Medical Applications

In articular joint implants, polymeric inserts are usually exploited for on-contact sliding surfaces to guarantee low friction and wear, a high load-bearing capacity, impact strength and stiffness, and biocompatibility. Surface micro-structuring can drastically reduce friction and wear by promoting hydrostatic friction due to synovial fluid. Ultra-High Molecular Weight Polyethylene (UHMWPE) is a suitable material for these applications due to its strong chemical resistance, excellent resistance to stress, cracking, abrasion, and wear, and self-lubricating property. However, surface micro-texturing of UHMWPE is hardly achievable with the currently available processes. The present study investigates UHMWPE's micro-textured surface replication capability via injection molding, comparing the results with the more easily processable High-Density Polyethylene (HDPE). Four different micro-texture cavities were designed and fabricated on a steel mold by micro-EDM milling, and used for the experimental campaign. Complete samples were fabricated with both materials. Then, the mold and samples were geometrically characterized, considering the dimensions of the features and the texture layout. The replication analysis showed that HDPE samples present geometrical errors that span from 1% to 9% resulting in an average error of 4.3%. In comparison, the UHMWPE samples display a higher variability, although still acceptable, with percentage errors ranging from 2% to 31% and an average error of 11.4%.

Helminth egg derivatives as proregenerative immunotherapies

The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth Schistosoma mansoni soluble egg antigen (SEA) to stimulate production of interleukin (IL)-4 and other type 2-associated cytokines without negative infection-related sequelae. The regenerative SEA (rSEA) applied to a murine muscle injury induced accumulation of IL-4-expressing T helper cells, eosinophils, and regulatory T cells and decreased expression of IL-17A in gamma delta (γδ) T cells, resulting in improved repair and decreased fibrosis. Encapsulation and controlled release of rSEA in a hydrogel further enhanced type 2 immunity and larger volumes of tissue repair. The broad regenerative capacity of rSEA was validated in articular joint and corneal injury models. These results introduce a regenerative immunotherapy approach using natural helminth derivatives.

Peroneal intraneural ganglion cyst with a nearly invisible joint connection (even to advocates of the articular theory): illustrative case.

The articular (synovial) theory describes the formation of intraneural ganglion cysts through defects in the capsule of synovial joints. While the articular theory is gaining significant traction in the literature, it is not universally accepted. Therefore, the authors present a case of a plainly visible peroneal intraneural cyst, although the subtle joint connection was not identified specifically at the time of surgery, with subsequent rapid extraneural cyst recurrence. The joint connection was not immediately evident on review of the magnetic resonance imaging, even to the authors who have a large experience with this clinical entity. The authors report this case to demonstrate that all intraneural ganglion cysts have joint connections, although they may be difficult to identify. An occult joint connection in the intraneural ganglion poses a unique diagnostic and management dilemma. High-resolution imaging is a valuable tool used to identify the articular branch joint connection as part of the surgical planning. Based on the articular theory, all intraneural ganglion cysts will have a joint connection through an articular branch, although this may be small or nearly invisible. Failure to appreciate this connection can lead to cyst recurrence. A high index of suspicion of the articular branch is needed for surgical planning.

Age and sex correlate with bony changes and anatomic variations of the lumbosacroiliac region of the vertebral column in a mixed population of horses.

To provide a postmortem description of anatomic variations and changes of the lumbosacroiliac region in horses. The authors hypothesized that lesion severity would increase with age and body weight and correlate to anatomic variations. Lumbosacroiliac vertebral specimens from 38 horses (mean age, 16 years; range, 5 to 30 years) that died or were euthanized for reasons unrelated to the study between November 2019 and October 2021. The lumbosacroiliac region of the vertebral column was removed from each cadaver. After dissection, disarticulation, and boiling, the anatomic specimens were examined for anatomic variations and osseous changes of the articular process joints (APJs), intertransverse joints (ITJs), and sacroiliac joints (SIJs). The lengths of L6-S1 intertransverse articular surfaces were measured and their ratios calculated. Descriptive statistics were obtained, and the χ2 test was used to assess differences in anatomic variations and abnormal changes of the APJs, ITJs, and SIJs. The most common anatomic variation was a sacrum-like shape of the transverse processes of L6 (29/38 [76%]) and converging orientation of dorsal spinous process of L6 (33/38 [87%]). The highest prevalence of bony changes was detected at L5-L6 (right, 34/38 [89%]; left, 33/38 [87%]) and L6-S1 APJs (right, 38/38 [100%]; left, 37/38 [97%]) and at SIJs (right, 32/38 [86%]; left, 31/38 [82%]). The shape of L6 transverse processes differed between breed (P = .01) and was associated with presence of L4-L5 ITJs (P < .01). Age and sex were associated with changes of the sacral dorsal spinous processes, ITJs, and APJs. The clinical significance of these findings could not be confirmed based on the study limitations.

Magnetic-Free Quaternion-Based Robust Unscented Kalman Filter for Upper Limb Kinematic Analysis

Human motion analysis is a field of increasing interest. In most applications, an accurate estimation of joint angles is needed. Inertial measurement units (IMUs) represent a very promising technology for motion capture. Unfortunately, their performances are strongly influenced by different sources of error (e.g., gyroscopes biases). To limit the effect of these sources of error, several algorithms (usually defined as “sensor fusion” algorithms) are used. The proposed work aims to validate a magnetic-free quaternion-based robust unscented Kalman filter (UKF) for upper limb kinematic analysis (i.e., estimation of the articular joint angles), using an inertial body sensor network, in a set of complex 3-D movements (i.e., the yoga poses). The algorithm was tested on ten expert yoga practitioners during the execution of the sun salutation sequence. Joint angle estimations were compared with the ones obtained from an optoelectronic reference system by evaluating the root mean square errors (RMSEs) and Pearson’s correlation coefficients. The achieved worst case was 8.41°, while the best one was 2.96° for RMSEs mean values. The accuracy of the algorithm was further confirmed by the high values of Pearson’s correlation coefficients (lowest mean value of 0.80). In addition, the comparison with one of the most used filters for attitude estimation [extended Kalman filter (EKF)] showed no significant differences between the two methods. Up to authors knowledge, the scientific literature lacks the development of a complete magnetic-free version of the UKF for human motion capture and analysis in complex movements, such as the one introduced here. The proposed work aims at filling this gap.

Post-traumatic osteoarthritis: A review of pathogenic mechanisms and novel targets for mitigation

Post-traumatic osteoarthritis (PTOA) develops secondary to a joint injury and accounts for 12 % of all osteoarthritis. These injuries, often of the lower extremity joints, occur due to trauma or accidents related to athletic or military activities. They primarily affect younger individuals although PTOA can occur across the spectrum of age. Pain and functional disability caused by PTOA confer a heavy economic toll on patients, in addition to detrimentally affecting their quality of life. Both high energy injuries that cause articular surface fracture with or without subchondral bone disruption and low-energy injuries involving joint dislocations or ligamentous injury cause PTOA, albeit through different mechanisms. Regardless, chondrocyte death, mitochondrial dysfunction, reactive oxygen species production, subchondral bone remodeling, inflammation and cytokine release in the cartilage and synovium play integral roles in the pathogenesis of PTOA. Evolving surgical methods are focused on stabilizing articular surface and joint structure congruity. However, to date there are no disease modifying medical therapies against PTOA. Increased recent understanding of the pathogenesis of the subchondral bone and synovial inflammation as well as that of chondrocyte mitochondrial dysfunction and apoptosis have led to the investigation of new therapeutics targeting these mechanisms to prevent or delay PTOA. This review discusses new advances in our understanding of cellular mechanisms underlying PTOA, and therapeutic approaches that are potentially effective in reducing the self-propagating cycle of subchondral bone alterations, inflammation, and cartilage degradation. Within this context, we focus therapeutic options involving anti-inflammatory and anti-apoptotic candidates that could prevent PTOA.