Bone Sclerosis Research Articles

Femoral head and acetabular necrosis combined with hip subluxation in people with HIV: a case report and literature review

IntroductionHIV is widely prevalent in all regions of the world. The use of antiretroviral drugs has dramatically reduced the mortality rate of HIV-related diseases, but correspondingly increased the incidence of chronic complications in HIV-positive people. Related studies have found that the incidence of osteonecrosis of the femoral head is higher in HIV-positive people, but the co-occurrence of femoral head necrosis, acetabular necrosis and hip joint dislocation in HIV-positive patients is rare.MethodsWe report a 50-year-old man with a 15-month history of progressively worsening right hip pain with movement restriction. According to the CT findings of the other hospital, the patient was admitted to the hospital with femoral head necrosis. After the admission, the relevant X-ray, CT and MRI examinations showed that the right femoral head collapsed and deformed, with the surrounding bone sclerosis, bone fragments, loose body of the joint, right hip subluxation, acetabular marginal osteogeny, and local microcystic degeneration. The left femoral head was in good shape, and cystic degeneration can be seen under the articular surface. The patient was finally diagnosed with femoral head necrosis and acetabular necrosis combined with hip subluxation.ResultsThe pain of the patient was significantly relieved after the operation, and the patient was discharged from the hospital one week after the start of treatment to continue rehabilitation training. During the follow-up one month after the operation, the self-reported pain disappeared completely, and the limitation of activity was significantly improved.

Forkhead box C1 promotes the pathology of osteoarthritis in subchondral bone osteoblasts via the Piezo1/YAP axis

Subchondral bone sclerosis is a key characteristic of osteoarthritis (OA). Prior research has shown that Forkhead box C1 (FoxC1) plays a role in the synovial inflammation of OA, but its specific role in the subchondral bone of OA has not been explored. Our research revealed elevated expression levels of FoxC1 and Piezo1 in OA subchondral bone tissues. Further experiments on OA subchondral bone osteoblasts with FoxC1 or Piezo1 overexpression showed increased cell proliferation activity, expression of Yes-associated Protein 1 (YAP) and osteogenic markers, and secretion of proinflammatory factors. Mechanistically, the overexpression of FoxC1 through Piezo1 activation, in combination with downstream YAP signaling, led to increased levels of alkaline phosphatase (ALP), collagen type 1 (COL1) A1, RUNX2, Osteocalcin, matrix metalloproteinase (MMP) 3, and MMP9 expression. Notably, inhibition of Piezo1 reversed the regulatory function of FoxC1. The binding of FoxC1 to the targeted area (ATATTTATTTA, residues +612 to +622) and the activation of Piezo1 transcription were verified by the dual luciferase assays. Additionally, Reduced subchondral osteosclerosis and microangiogenesis were observed in knee joints from FoxC1-conditional knockout (CKO) and Piezo1-CKO mice, indicating reduced lesions. Collectively, our study reveals the significant involvement of FoxC1 in the pathologic process of OA subchondral bone via the Piezo1/YAP signaling pathway, potentially establishing a novel therapeutic target.

The Multifaceted Protective Role of Nuclear Factor Erythroid 2-Related Factor 2 in Osteoarthritis: Regulation of Oxidative Stress and Inflammation.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of joint cartilage, subchondral bone sclerosis, synovitis, and structural changes in the joint. Recent research has highlighted the role of various genes in the pathogenesis and progression of OA, with nuclear factor erythroid 2-related factor 2 (NRF2) emerging as a critical player. NRF2, a vital transcription factor, plays a key role in regulating the OA microenvironment and slowing the disease's progression. It modulates the expression of several antioxidant enzymes, such as Heme oxygenase-1 (HO-1) and NAD(P)H oxidoreductase 1 (NQO1), among others, which help reduce oxidative stress. Furthermore, NRF2 inhibits the nuclear factor kappa-B (NF-κB) signaling pathway, thereby decreasing inflammation, joint pain, and the breakdown of cartilage extracellular matrix, while also mitigating cell aging and death. This review discusses NRF2's impact on oxidative stress, inflammation, cell aging, and various cell death modes (such as apoptosis, necroptosis, and ferroptosis) in OA-affected chondrocytes. The role of NRF2 in OA macrophages, and synovial fibroblasts was also discussed. It also covers NRF2's role in preserving the cartilage extracellular matrix and alleviating joint pain. The purpose of this review is to provide a comprehensive understanding of NRF2's protective mechanisms in OA, highlighting its potential as a therapeutic target and underscoring its significance in the development of novel treatment strategies for OA.

Postnatal deletion of Phlpp1 in chondrocytes delays post-traumatic osteoarthritis in male mice

ObjectiveOsteoarthritis is a chronic, debilitating disease that causes long-term pain and immobility. Germline deletion of Phlpp1 or administration of small molecules that inhibit Phlpp1 prevents post-traumatic osteoarthritis (PTOA) in mice. However, the chondrocyte-intrinsic role of Phlpp1 in PTOA progression is unknown. The objective of this study was to determine how postnatal, chondrocyte-directed deletion of Phlpp1 affects PTOA progression in the presence or absence of Phlpp inhibitors. DesignPhlpp1fl/fl; Agc-CreERT2 and Agc-CreERT2 mice were injected with tamoxifen at 12 weeks of age to generate Phlpp1-CKOAgcERT and control (AgcERT) groups. Male mice underwent surgery to destabilize the medial meniscus (DMM) at 17 weeks of age. A separate cohort of male Phlpp1-CKOAgcERT mice were administered an intra-articular injection of NSC117079, a Phlpp1/2 inhibitor, or saline seven weeks after DMM surgery. Activity and mechanical allodynia were monitored throughout the experiment and cartilage damage was evaluated 12 weeks post-surgery. ResultsPhlpp1-CKOAgcERT mice had less cartilage damage than AgcERT littermates 12 weeks after DMM surgery but exhibited no differences in activity. Prg4 expression was also higher in articular chondrocytes of Phlpp1-CKOAgcERT mice. Intra-articular administration of NSC117079 to Phlpp1-CKOAgcERT mice improved cartilage structure, subchondral bone sclerosis, and mechanical allodynia at 12 weeks post-DMM. ConclusionsPostnatal deletion of Phlpp1 in chondrocytes attenuates DMM-induced cartilage damage and subchondral bone sclerosis but does not prevent pain-related behaviors. Intra-articular injection of Phlpp inhibitors delays mechanical allodynia in Phlpp1-CKOAgcERT mice. These data indicate that Phlpp1 in chondrocytes affects articular cartilage structure after injury, but pain-related behaviors are controlled by Phlpp1 or Phlpp2 in other cell types.

Slit3 by PTH-Induced Osteoblast Secretion Repels Sensory Innervation in Spine Porous Endplates to Relieve Low Back Pain.

During aging, the spine undergoes degenerative changes, particularly with vertebral endplate bone expansion and sclerosis, that is associated with nonspecific low back pain (LBP). We reported that parathyroid hormone (PTH) treatment could reduce vertebral endplate sclerosis and improve pain behaviors in aging, SM/J and young lumbar spine instability (LSI) mice. Aberrant innervation noted in the vertebral body and endplate during spinal degeneration was reduced with PTH treatment in aging and LSI mice as quantified by PGP9.5 + and CGRP + nerve fibers, as well as CGRP expression in dorsal root ganglia (DRG). The neuronal repulsion factor Slit3 significantly increased in response to PTH treatment mediated by transcriptional factor FoxA2. PTH type1 receptor (PPR) and Slit3 deletion in osteoblasts prevented PTH-reduction of endplate porosity and improvement in behavior tests, whereas PPR deletion in chondrocytes continued to respond to PTH. Altogether, PTH stimulates Slit3 to repel sensory nerve innervation and provides symptomatic relief of LBP associated with spinal degeneration.

Imaging of Sacroiliac Pain: The Current State-of-the-Art.

Pain in the sacroiliac (SI) region is a common clinical manifestation, often caused by diseases involving the SI joints. This is typically due to inflammation or degenerative changes, while infections or cancer are less frequent causes. The SI joint is challenging to image accurately because of its distinct anatomical characteristics. For an accurate diagnosis, conventional radiography often needs to be supplemented with more precise methods such as magnetic resonance imaging (MRI) or computed tomography (CT). Sacroiliitis, a common presenting feature of axial spondyloarthritis (axial SpA), manifests as bone marrow edema, erosions, sclerosis, and joint space narrowing. Septic sacroiliitis and repetitive stress injuries in sports can also cause changes resembling inflammatory sacroiliitis. Other conditions, such as osteitis condensans ilii (OCI), can mimic the radiologic characteristics of sacroiliitis. Inflammatory lesions are diagnosed by concurrent erosions, hyperostosis, and ankylosis. Ligament ossifications or mechanical stress can also result in arthritic disorders. Determining the exact diagnosis can be aided by the distribution of the lesions. Inflammatory lesions can affect any part of the articulation, including the inferior and posterior portions. Mechanical lesions, such as those seen in OCI, often occur in the anterior middle region of the joint. In cases of idiopathic skeletal hyperostosis, ligament ossification is found at the joint borders. This pictorial essay describes common SI joint problems, illustrated with multimodal imaging data. We, also, discuss strategies for selecting the best imaging modalities, along with imaging pitfalls, key points, and approaches for treating patients with suspected inflammatory back pain.

Significant overlap of inflammatory and degenerative features on imaging among patients with degenerative disc disease, diffuse idiopathic skeletal hyperostosis and axial spondyloarthritis: a real-life cohort study

BackgroundDifferentiating between degenerative disc disease (DDD), diffuse idiopathic skeletal hyperostosis (DISH), and axial spondyloarthritis (axSpA) represents a diagnostic challenge in patients with low back pain (LBP). We aimed to evaluate the distribution of inflammatory and degenerative imaging features in a real-life cohort of LBP patients referred to a tertiary university rheumatology center.MethodsIn a retrospective cross-sectional analysis of patients referred for LBP, demographics, symptom information, and available imaging were collected. SpA-like changes were considered in the spine in the presence of one of the following lesions typically related to SpA: erosions, sclerosis, squaring, and syndesmophytes on conventional radiographs (CR) and bone marrow oedema (BMO), erosions, sclerosis, and fat lesions (FL) on MRI. SIJ CR were graded per New York criteria; on MRIs, SIJs were evaluated by quadrant for BMO, erosions, FL, sclerosis and ankylosis, similar to the approach used by the Berlin SIJ MRI scoring system. The final diagnosis made by the rheumatologist was the gold standard. Data were presented descriptively, by patient and by quadrant, and compared among the three diagnosis groups.ResultsAmong 136 referred patients, 71 had DDD, 38 DISH, and 27 axSpA; median age 62 years [IQR55-73], 63% males. On CR, SpA-like changes were significantly higher in axSpA in the lumbar (50%, vs. DDD 23%, DISH 22%), in DISH in the thoracic (28%, vs. DDD 8%, axSpA 12%), and in DDD in the cervical spine (67% vs. DISH 0%, axSpA 33%). On MRI, BMO was significantly higher in DISH in the thoracic (37%, vs. DDD 22%, axSpA 5%) and equally distributed in the lumbar spine (35-42%). FL were significantly more frequently identified in DISH and axSpA in the thoracic (56% and 52%) and DDD and axSpA in the lumbar spine (65% and 74%, respectively). Degenerative changes were frequent in the three groups. Sacroiliitis (NY criteria) was identified in 49% (axSpA 76%, DDD 48%, DISH 29%).ConclusionA significant overlap was found among DDD, DISH, and axSpA for inflammatory and degenerative imaging features. Particularly, SpA-like spine CR features were found in one-fourth of patients with DISH, and MRI BMO was found in one-third of those patients.

Detection Ewingella americana from a patient with Andersson lesion in ankylosing spondylitis by metagenomic next-generation sequencing test: a case report

BackgroundAndersen’s lesion (AL) is a rare complication of ankylosing spondylitis (AS), characterized by nonneoplastic bone destruction, typically manifested as bone destruction and sclerosis in the vertebral body and/or intervertebral disc area. At present, there is no consensus on the pathology and etiology of AL. Repeated trauma, inflammation in essence and part of the natural history of Ankylosing spondylitis itself are the most widely recognized theories of the etiology of AL. However, positive bacteria cultured in bone biopsy of Andersen’s lesion (AL) in Ankylosing spondylitis patients are extremely rare. Herein, we report a rare case of detecting Ewingella americana from a patient with Andersson lesion in ankylosing spondylitis by Metagenomic Next-Generation Sequencing (mNGS) Test.Case presentationThis case involved a 39-year-old male with a history of AS for 11 years, who developed AL (T11/12) in the thoracic vertebrae. After sufficient preoperative preparation, we successfully performed one-stage posterior approach corrective surgery and collected bone biopsies samples for examination. Cultured bacteria were not found, and pathological histology indicated infiltration of inflammatory cells. However, it is worth noting that we discovered a gram-negative bacterium, the Ewingella americana, through mNGS testing. Further histopathological examination suggests chronic inflammatory cell infiltration. After one-stage posterior approach corrective surgery, the patient’s condition significantly improved. At the 6-month follow-up, the pain significantly decreased, and the patient returned to normal life.ConclusionWe detected Ewinia americana in the bone biopsies of Andersson lesion (AL) in ankylosing spondylitis patient by mNGS.

Concurrent Joint Contact in Anterior Cruciate Ligament Injury induces cartilage micro-injury and subchondral bone sclerosis, resulting in knee osteoarthritis.

Anterior Cruciate Ligament (ACL) injury initiates post-traumatic osteoarthritis (PTOA) via two distinct processes: initial direct contact injury of the cartilage surface during ACL injury, and secondary joint instability due to the ACL deficiency. Using the well-established Compression-induced ACL rupture method (ACL-R) and a novel Non-Compression ACL-R model, we aimed to reveal the individual effects of cartilage compression and joint instability on PTOA progression after ACL injury in mice. Twelve-week-old C57BL/6J male were randomly divided to three experimental groups: Compression ACL-R, Non-Compression ACL-R, and Intact. Following ACL injury, we performed joint laxity testing and microscopic analysis of the articular cartilage surface at 0 days, in vivo optical imaging of matrix-metalloproteinase (MMP) activity at 3 and 7 days, and histological and microCT analysis at 0, 7, 14, and 28 days. The Compression ACL-R group exhibited a significant increase of cartilage roughness immediately after injury compared with the Non-Compression group. At 7 days, the Compression group exhibited increased MMP-induced fluorescence intensity and MMP-13 positive cell ratio of chondrocytes. Moreover, histological cartilage degeneration was observable in the Compression group at the same time point. Sclerosis of tibial subchondral bone in the Compression group was more significantly developed than in the Non-Compression group at 28 days. Both Compression and Non-Compression ACL injury initiated PTOA progression due to joint instability. However, joint contact during ACL rupture also caused initial micro-damage on the cartilage surface and initiated early MMP activity, which could accelerate PTOA progression compared to ACL injury without concurrent joint contact.

Treatment of osteoarthritis by implantation of Mg- and WE43-cylinders - A preclinical study on bone and cartilage changes and their influence on pain sensation in rabbits

With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritis represents a multifactorial disease with no effective treatment options. As biomechanical shift in the trabecular network may be a driver for further cartilage degeneration, bone enhancement could possibly delay OA progression. Magnesium is known to be osteoconductive and already showed positive effects in OA models. We aimed to use magnesium cylinders to enhance subchondral bone quality, condition of cartilage and pain sensation compared to sole drilling in vivo. After eight weeks of implantation in rabbits, significant increase in subchondral bone volume and trabecular thickness with constant bone mineral density was found indicating favored biomechanics. As representative for pain, a higher number of CD271+ vessels were present in control samples without magnesium. However, this result could not be confirmed by sensitive, objective lameness evaluation using a pressure sensing mat and no positive effect could be shown on either cartilage degeneration evaluated by OARSI score nor the presence of regenerative cells in CD271-stained samples. The presented results show a relevant impact of implanted magnesium on key structures in OA pain with missing clinical relevance regarding pain. Further studies with shifted focus should examine additional structures as joint capsule or osteophytes.

Influence on the temporomandibular joint induced by mandibular malpositioning caused by vertical dimension elevation and occlusal loss in adult rats: An imaging, histological and immunohistochemical study.

Mandibular malpositioning may result in an abnormal concentration of stresses within the temporomandibular joint (TMJ) in adult rats, which may further lead to a series of pathological changes, such as articular cartilage wear, subchondral bone sclerosis and osteophyte formation. However, the pathological and adaptive changes in condylar cartilage caused by different stress distributions are still controversial. The aim of this study was to observe the effect of sagittal changes in mandibular position on condylar cartilage by changing the occlusal vertical dimension (OVD) in adult rats. Fifteen-week-old female rats were divided into three groups: control (CON), increased OVD (iOVD) and loss of occlusion (LO) groups. An occlusal plate and tooth extraction were used to establish the animal model. TMJ samples of the experimental and CON groups were observed and investigated by bone morphological, histomorphological and immunohistochemical staining analyses at 3 days, 1 week, 2 weeks, 4 weeks and 8 weeks. Weight curves were plotted. Micro-computed tomography showed that, compared with the CON group, cartilage destruction followed by repair occurred in both experimental groups, which was similar to the trend observed in haematoxylin-eosin staining. All experimental results for the iOVD group showed an approximately similar time trend. Compared with the iOVD group, the toluidine blue and immunohistochemical staining results in the LO group showed no obvious change trend over time. Compared with occlusal loss, an increase in OVD caused faster and more severe damage to condylar cartilage, and subchondral bone repair occurred later.

Outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning.

To report the outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning (FGNMP). Retrospective case series. A total of 15 client owned dogs and two cats with 57 metabone fractures. Description of FGNMP and reporting of the following data: signalment, pre- and postoperative radiographs, intramedullary pin diameter used, anesthesia, surgery and coaptation times, duration to normal weightbearing and bone union, postoperative care and complications. Median surgery time was 54 min (range: 26-99), median duration of coaptation was 14 days (range: 1-5 weeks), median time to normal weightbearing was 16 days (range: 2-45) and median time to bone union was 6 weeks (range: 4-12). All cases had at least 12 months of post-surgical follow-up with a median follow-up of 18 months (range: 12-70). No major complications occurred. Mild radiographic changes associated with subchondral bone sclerosis were noted on follow-up radiographs in 13/57 fractures. All cases returned to normal gait and full (15) or acceptable (2) function. In this study, FGNMP was an effective and safe technique for metabone fracture repair, requiring only short-term external coaptation in most patients. Time to bone union and return to normal function compared favorably to previously reported techniques. Fluoroscopically guided normograde metabone pinning provides an alternative technique for treatment of metabone fractures.

Distinctiveness of Femoral and Acetabular Mesenchymal Stem and Progenitor Populations in Patients with Primary and Secondary Hip Osteoarthritis Due to Developmental Dysplasia.

Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management.

Navicular bone oedema and sclerosis: current concepts on best management

Pathology associated with the navicular bone remains a common cause of forelimb lameness in horses. Since the introduction of advanced imaging modalities (particularly magnetic resonance imaging) it is now recognised that pathology of the navicular bone rarely occurs in isolation; concurrent abnormalities of the structures of the podotrochlear apparatus are often present. Different pathological processes of the navicular bone can have the same radiological appearance. Identifying the underlying disease process, as well as concurrent injuries, is essential for implementing the most appropriate management strategies in horses with navicular bone pathology. Horses with acute onset lameness or soft tissue injuries will often require a period of rest initially, whereas horses with chronic insidious lameness and no soft tissue pathology may be able to continue in work following treatment. Management should be focused on reduction of pain and inflammation which is often achieved with systemic non-steroidal anti-inflammatories, and intra-articular or intra-bursal medication in combination with reducing concussive forces acting on the navicular bone through alterations in shoeing and modification of exercise.

Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Radix Rehmanniae Praeparata - Angelica Sinensis - Radix Achyranthis Bidentatae in Treating Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA. The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK-8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments. In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats. RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.

Exploring the pharmacological mechanism of Glycyrrhiza uralensis against KOA through integrating network pharmacology and experimental assessment.

Knee osteoarthritis (KOA), a major health and economic problem facing older adults worldwide, is a degenerative joint disease. Glycyrrhiza uralensis Fisch. (GC) plays an integral role in many classic Chinese medicine prescriptions for treating knee osteoarthritis. Still, the role of GC in treating KOA is unclear. To explore the pharmacological mechanism of GC against KOA, UPLC-Q-TOF/MS was conducted to detect the main compounds in GC. The therapeutic effect of GC on DMM-induced osteoarthritic mice was assessed by histomorphology, μCT, behavioural tests, and immunohistochemical staining. Network pharmacology and molecular docking were used to predict the potential targets of GC against KOA. The predicted results were verified by immunohistochemical staining Animal experiments showed that GC had a protective effect on DMM-induced KOA, mainly in the improvement of movement disorders, subchondral bone sclerosis and cartilage damage. A variety of flavonoids and triterpenoids were detected in GC via UPLC-Q-TOF/MS, such as Naringenin. Seven core targets (JUN, MAPK3, MAPK1, AKT1, TP53, RELA and STAT3) and three main pathways (IL-17, NF-κB and TNF signalling pathways) were discovered through network pharmacology analysis that closely related to inflammatory response. Interestingly, molecular docking results showed that the active ingredient Naringenin had a good binding effect on anti-inflammatory-related proteins. In the verification experiment, after the intervention of GC, the expression levels of pp65 and F4/80 inflammatory indicators in the knee joint of KOA model mice were significantly downregulated. GC could improve the inflammatory environment in DMM-induced osteoarthritic mice thus alleviating the physiological structure and dysfunction of the knee joint. GC might play an important role in the treatment of knee osteoarthritis.

Underlying bone change in oral squamous cell carcinoma observed from magnetic resonance imaging and computed tomography: Potential implications for tumor aggressiveness and prognosis

Background/purposeIn cases where oral squamous cell carcinoma (OSCC) invades the jawbone, clinicians frequently observe abnormal attenuation on computed tomography (CT) and pathologic signal intensity (SI) on magnetic resonance (MR) imaging of the affected underlying bone marrow. This study introduced a concept of “underlying bone change” to examine its association with clinicopathological features and prognosis of OSCC, as well as its correlation with medullary invasion. Materials and methodsWe enrolled 93 consecutive patients diagnosed with OSCC, who underwent mandibulectomy between 2010 and 2016. CT and MR images, along with electronic medical records, were reviewed to evaluate correlations between underlying bone changes, clinicopathological features, five-year overall survival, and medullary invasion. ResultsOf the 93 patients, 69 (74.2%) exhibited underlying bone sclerosis on CT, and 74 (79.6%) displayed pathological SI on MR images. These underlying bone changes correlated with the T stage and recurrence, but not with overall survival.Medullary invasion, observed in 61 (65.6%) patients, was strongly associated with T and TNM stages and was linked to poorer overall survival.The underlying bone changes on CT and MR images were positively associated with medullary invasion; however, no significant differences were found in the occurrence of underlying bone changes between the subtypes based on the extent of medullary invasion. ConclusionUnderlying bone changes on CT and MR images can provide valuable insights into the aggressiveness of bone invasion by OSCC. Accurate interpretation of these imaging findings might be crucial for correctly delineating surgical margins and preventing the overestimation of tumor extent.

Engineered Exosomes with ATF5-Modified mRNA Loaded in Injectable Thermogels Alleviate Osteoarthritis by Targeting the Mitochondrial Unfolded Protein Response.

Osteoarthritis (OA) progression is highly associated with chondrocyte mitochondrial dysfunction and disorders of catabolism and anabolism of the extracellular matrix (ECM) in the articular cartilage. The mitochondrial unfolded protein response (UPRmt), which is an integral component of the mitochondrial quality control (MQC) system, is essential for maintaining chondrocyte homeostasis. We successfully validated the pivotal role of activating transcription factor 5 (ATF5) in upregulating the UPRmt, mitigating IL-1β-induced inflammation and mitochondrial dysfunction, and promoting balanced metabolism in articular cartilage ECM, proving its potential as a promising therapeutic target for OA. Modified mRNAs (modRNAs) have emerged as novel and efficient gene delivery vectors for nucleic acid therapeutic approaches. In this study, we combined Atf5-modRNA (modAtf5) with engineered exosomes derived from bone mesenchymal stem cells (ExmodAtf5) to exert cytoprotective effects on chondrocytes in articular cartilage via Atf5. However, the rapid localized metabolization of ExmodAtf5 limits its application. PLGA-PEG-PLGA (Gel), an injectable thermosensitive hydrogel, was used as a carrier of ExmodAtf5 (Gel@ExmodAtf5) to achieve a sustained release of ExmodAtf5. In vitro and in vivo, the use of Gel@ExmodAtf5 was shown to be a highly effective strategy for OA treatment. The in vivo therapeutic effect of Gel@ExmodAtf5 was evidenced by the preservation of the intact cartilage surface, low OARSI scores, fewer osteophytes, and mild subchondral bone sclerosis and cystic degeneration. Consequently, the combination of ExmodAtf5 and PLGA-PEG-PLGA could significantly enhance the therapeutic efficacy and prolong the exosome release. In addition, the mitochondrial protease ClpP enhanced chondrocyte autophagy by modulating the mTOR/Ulk1 pathway. As a result of our research, Gel@ExmodAtf5 can be considered to be effective at alleviating the progression of OA.

Bone pattern changes in post liver transplant patients using bisphosphonates.

To identify radiographic findings suggestive of drug-induced osteonecrosis and evaluate radiomorphometric patterns indicative of changes in bone mineral density in individuals transplanted for liver disorders using bisphosphonates. The study group included panoramic x-rays of liver transplant patients who are being monitored and who present a clinical status of osteoporosis and use bisphosphonates. The control group was made up of liver transplant patients who did not have osteoporosis. On panoramic radiographs, mental index (MI) and mandibular cortical index (MCI) and the presence of radiographic anomalies suggestive of osteonecrosis were evaluated. There were significant statistical results when comparing the groups in relation to the decrease in bone mineral density (BMD) with MCI-C3 (p=0.036), however, there were none in relation to MI (p=0.14). There were no valid statistical results when relating MCI (p=0.94) and MI (p=0.66) with reduced BMD and use of bisphosphonates. Liver transplant individuals using bisphosphonates present greater radiographic signs of bone sclerosis suggestive of a greater propensity to develop osteonecrosis of the jaw and an increased risk of presenting changes suggestive of reduced bone mineral density on panoramic radiographs when compared to liver transplant individuals not using bisphosphonates.

The common marmoset as a translational model of age-related osteoarthritis.

Age-related osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes in nearly every intra- and peri-articular tissue that contributes to disability in older adults. Studying the etiology of age-related OA in humans is difficult due to an unpredictable onset and insidious nature. A barrier in developing OA modifying therapies is the lack of translational models that replicate human joint anatomy and age-related OA progression. The purpose of this study was to determine whether the common marmoset is a faithful model of human age-related knee OA. Semi-quantitative microCTscoring revealed greater radiographic OA in geriatric versus adult marmosets, and the age-related increase in OA prevalence was similar between marmosets and humans. Quantitative assessments indicate greater medial tibial cortical and trabecular bone thickness and heterogeneity in geriatric versus adult marmosets which is consistent with an age-related increase in focal subchondral bone sclerosis. Additionally, marmosets displayed an age-associated increase in synovitis and calcification of the meniscus and patella. Histological OA pathology in the medial tibial plateau was greater in geriatric versus adult marmosets driven by articular cartilage damage, proteoglycan loss, and alteredchondrocyte cellularity. The age-associated increase in medial tibial cartilage OA pathology and meniscal calcification was greater in female versus male geriatric marmosets. Overall, marmosets largely replicate human OA as evident by similar 1) cartilage and skeletal morphology, 2) age-related progression in OA pathology, and 3) sex differences in OA pathology with increasing age. Collectively, these data suggest that the common marmoset is a highly translatable model ofthe naturally occurring, age-related OA seenin humans.