Degeneration Of Subchondral Bone Research Articles

Subchondral Bone Degeneration and Pathology 3-15 Years Following Ankle Sprain Injury in Adolescent Sport.

Sport-related ankle sprains (SASs) are prevalent in adolescents (ages 10-19), increasing the risk of developing posttraumatic osteoarthritis (PTOA). Although early ankle osteoarthritis (OA) is not well defined, OA eventually includes alterations in bone mineral density (BMD), structural changes, and soft tissue pathology. This study examined the impact of SAS sustained in adolescent sport on bone and soft tissue structural outcomes 3-15 years postinjury. Participants (n = 10) with prior unilateral SAS in adolescent sport (HxAI) were compared to age- and sex-matched controls. To assess injury-related pathologies and BMD, 1.5-tesla (T) extremity magnetic resonance imaging (MRI) and computed tomography scans were used. Semiquantitative scores for injury patterns and OA features from MRI scans were summed and compared between groups. The talus, calcaneus, navicular, and 5% distal tibia were segmented, and BMD was measured for each bone. All HxAI participants exhibited MRI injury pathology (median 2; IQR 1-6), whereas only 1 of 10 controls showed pathology (median 0; IQR 0-0), χ2(1, n = 20) = 16.36, P < .001. Both the injured and uninjured ankles in HxAI displayed injury pattern pathology. Additionally, 3 of 10 injured ankles and 2 of 10 uninjured ankles in the HxAI group (median 0; IQR 0-3), but none of the controls (median 0; IQR 0-0), exhibited OA features. In the HxAI group, talus BMD was lower in the injured ankle (502.4 ± 67.9 g/cm3) compared with the uninjured ankle (515.6 ± 70.1 g/cm3) (F = 13.33, P = .002), with no significant BMD differences at the calcaneus, navicular, or 5% distal tibia. No differences were observed between the ankles of the control group. The presence of injury pattern pathology, structural changes, and reduced talus BMD suggest that degenerative changes may occur in individuals as early as 3-15 years following ankle injury.

Human umbilical cord mesenchymal stem cells on treating osteoarthritis in a rabbit model: Injection strategies

Human umbilical cord mesenchymal stem cells (UCMSCs) are a novel stem-cell source to treat osteoarthritis (OA). Here we investigated the therapeutic effects of UCMSCs injection strategies on knee OA in a rabbit model. Thirty OA rabbits randomly received normal saline, a single dose of 1 × 106 UCMSCs, or three injections of 1 × 106 UCMSCs at 2, 4, 6 weeks. Articular cartilages were collected after 8 weeks. Macroscopic and histological assessments indicated that intra-articular injection of UCMSCs, both single and multiple injection, significantly reduced the formation of periarticular osteophytes and articular cartilage degeneration when compared with the control. Furthermore, both UCMSCs injections increased the expression of chondrogenic markers in the articular cartilage, and reduced the levels of TNF-α and IL-6 in synovium. Micro-CT showed significant reduction of sub-chondral bone degeneration and osteophytes in the multiple-injection group compared to the control and single-injection group. Taken together, intra-articular injection of UCMSCs for OA treatment is safe and effective. Single and multiple injection of UCMSCs had comparable reparative effect on cartilage lesions, while multiple injection of UCMSCs further exerted effect on enhancing subchondral bone volume.

Mass Spectrometry Imaging of the Subchondral Bone in Osteoarthritis Reveals Tissue Remodeling of Extracellular Matrix Proteins that Precede Cartilage Loss.

Osteoarthritis (OA) of the knee is a degenerative condition of the skeletal extracellular matrix (ECM) marked by the loss of articular cartilage and subchondral bone homeostasis. Treatments for OA in the knee beyond full joint replacement are lacking primarily due to gaps in molecular knowledge of the biological drivers of disease. Here, Mass Spectrometry Imaging (MSI) enabled molecular spatial mapping of the proteomic landscape of human knee tissues. Histologic sections of human tibial plateaus from OA patients and cadaveric controls were treated with collagenase III to target ECM proteins prior to imaging using a timsTOF fleX mass spectrometer (Bruker) for matrix-assisted laser desorption ionization (MALDI)-MSI of bone and cartilage proteins in human knees. Spatial MSI data of the knee, using sections of the tibial plateau from non-arthritic, cadaveric donors or from knee replacement patients with medial OA were processed and automatically segmented identifying distinct areas of joint damage. ECM peptide markers compared either OA to cadaveric tissues or OA medial to OA lateral. Not only did candidate peptides distinguish OA relative to intact cartilage, but also emphasized a significant spatial difference between OA and intact subchondral bone (AUROC >0.85). Overall, 31 peptide candidates from ECM proteins, including COL1A1, COL3A1, and unanticipated detection of collagens COL6A1 and COL6A3 in adult bone, exhibited significantly elevated abundance in diseased tissue. Highly specific hydroxyproline-containing collagens dominated OA subchondral bone directly under regions of lost cartilage revealing dramatic tissue remodeling providing molecular details on the progression of joint degeneration in OA. The identification of specific spatial markers for the progression of subchondral bone degeneration in OA advances our molecular understanding of coupled deterioration of joint tissues.

Shear wave ultrasound elastography for estimating cartilage stiffness: implications for early detection of osteoarthritis

Current osteoarthritis (OA) diagnosis relies on radiographic abnormalities found in later stages of the disease, posing a challenge to the treatment efficacy. Therefore, earlier detection of OA is essential for improving therapeutic outcomes. The aim of this study was to investigate the feasibility of shear wave ultrasound elastography (SWUE) to detect changes in cartilage mechanical properties under OA conditions ex-vivo. Bovine osteochondral units were harvested from femoral condyles and subjected to either trypsin degradation, cartilage surface roughness defect using varying degrees of sandpaper, or subchondral bone degeneration using formic acid (FA) injection. Shear waves were generated using a mechanical shaker, while a high-frequency ultrasound system operating at 18 MHz was employed to detect wave propagation along the samples. The elasticity of cartilage was estimated by the shear wave speed (SWS) through the auto-correlation method. Our results show that the estimated SWS of cartilage after 24, 48, and 72 hours of trypsin incubation significantly decreased by 37%, 43%, and 59%, respectively, compared to the control group. Surface roughness treatment using 150-grit sandpaper significantly decreased the SWS by 35% compared to the control. Samples treated with 7% FA showed a significant increase in SWS by 62%, 89%, and 53% compared to control, 1% FA, and 3% FA, respectively. Our findings demonstrate the feasibility of SWUE to differentiate the elastic properties of cartilage under different OA conditions. This study presents the potential of a noninvasive, nonionizing tool for early detection of OA, representing a significant step toward its clinical implementation.Graphical

Electroacupuncture improves motor function of rats with osteoarthritis by alleviating joint inflammation through the Wnt-7B/β-catenin signaling pathway

To investigate the effect of electroacupuncture on osteoarthritis in rats and explore the possible mechanism. Thirty SD rats were randomly divided into osteoarthritis model group, electro-acupuncture group and control group (n=10), and in the former two groups, early osteoarthritis was induced using a modified DMM surgical modeling method. After successful modeling, the rats in the electro-acupuncture group were treated with electro-acupuncture at bilateral "Housanli" and "Anterior knee point". Behavioral tests of the rats were performed and scored using the LequesneMG scale. Subchondral bone degeneration was observed in each group, and serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP were measured using ELISA. The mRNA and protein expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7, and MMP-3 in the cartilage tissue of the knee joints were detected using RT-PCR and Western blotting. In behavioral tests, the rats in the model and electroacupuncture groups had significantly higher LequesneMG scores after modeling than those in the control group (P < 0.05). After 20 days of treatment, LequesneMG scores were significantly lowered in rats in the electroacupuncture as compared with the model rats (P < 0.05). Imaging examination revealed obvious subchondral bone damage in both the electroacupuncture group and the model group, but the damages were significantly milder with former group. Compared with the model rats, the rats receiving electroacupuncture had significantly lower serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP (P < 0.05) with also lower expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7 and MMP-3 in the cartilage tissues at both the mRNA and protein levels (P < 0.05). Electroacupuncture can alleviate joint pain and improve subchondral bone damage in rats with osteoarthritis by reducing IL-1β levels in the joint cartilage tissue and serum to alleviate joint inflammation and by reducing such cytokines as ADAMTS-7 and MMP-3 via regulating the Wnt-7B/β-catenin signaling pathway.

Bone marrow lesions in osteoarthritis: From basic science to clinical implications

Osteoarthritis (OA) is the most prevalent musculoskeletal disease characterized by multiple joint structure damages, including articular cartilage, subchondral bone and synovium, resulting in disability and economic burden. Bone marrow lesions (BMLs) are common and important magnetic resonance imaging (MRI) features in OA patients. Basic and clinical research on subchondral BMLs in the pathogenesis of OA has been a hotspot. New evidence shows that subchondral bone degeneration, including BML and angiogenesis, occurs not only at or after cartilage degeneration, but even earlier than cartilage degeneration. Although BMLs are recognized as important biomarkers for OA, their exact roles in the pathogenesis of OA are still unclear, and disputes about the clinical impact and treatment of BMLs remain. This review summarizes the current basic and clinical research progress of BMLs. We particularly focus on molecular pathways, cellular abnormalities and microenvironmental changes of subchondral bone that contributed to the formation of BMLs, and emphasize the crosstalk between subchondral bone and cartilage in OA development. Finally, potential therapeutic strategies targeting BMLs in OA are discussed, which provides novel strategies for OA treatment.

MiR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway.

Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients.

Morphological and mechanical alterations in articular cartilage and subchondral bone during spontaneous hip osteoarthritis in guinea pigs.

Objectives: This study aimed to investigate the morphological and mechanical changes in articular cartilage and subchondral bone during spontaneous hip osteoarthritis in guinea pigs. Materials and methods: Hip joints of guinea pigs were investigated at 1, 3, 6, and 9 months of age (hereafter denoted as 1M, 3M, 6M, and 9M, respectively; n = 7 in each group). Morphological and mechanical alterations during spontaneous hip osteoarthritis in guinea pigs were investigated. The alterations included the micromechanical properties of articular cartilage (stiffness and creep deformation), microstructure of the subchondral bone (bone mineral density, bone volume fraction, trabecular thickness, trabecular number, and trabecular separation), micromorphology of the articular cartilage, and surface nanostructure (grain size and roughness) of the articular cartilage and subchondral bone. Results: Micromechanical properties of articular cartilage in 1M showed the lowest stiffness and highest creep deformation with no significant differences in stiffness or creep deformation amongst 3M, 6M, and 9M. Articular cartilage thickness decreased with age. The earliest degeneration of articular cartilage occurred at 6 months of age, characterised by surface unevenness and evident chondrocytes reduction in micromorphology, as well as increased grain size and decreased roughness in nanostructure. No degeneration at micro- or nanostructure of subchondral bone was observed before 9 months. Conclusion: Morphological degeneration of cartilage occurred before degeneration of mechanical properties. Meanwhile, degeneration of cartilage occurred before degeneration of subchondral bone during hip osteoarthritis. The current study provided novel insights into the structural and micromechanical interaction of hip osteoarthritis, which can serve as a theoretical basis for understanding the formation and progression of osteoarthritis.

The value of the glenohumeral joint cross-sectional area as a morphological parameter of glenohumeral osteoarthritis.

Glenohumeral joint (GHJ) space narrowing has been demonstrated to be an important morphologic parameter of glenohumeral osteoarthritis (GHO). However, the morphology of GHJ space is irregular because of degeneration of subchondral bone and articular cartilage. Thus, we devised GHJ cartilage cross-sectional area (GHJCCSA) as a new diagnostic morphological parameter to assess the irregular morphologic change of GHJ. GHJ samples were acquired from 33 patients with GHO and from 33 normal controls without evidence of GHO based on shoulder magnetic resonance imaging. T2-weighted coronal MRIs were collected at the GHJ level for all individuals. GHJCCSA and GHJ cartilage thickness (GHJCT) at the GHJ were measured on MRIs using a graphic measuring system. The GHJCCSA was measured as the whole cartilage cross-sectional area of the GHJ. The average GHJCCSA was 115.28 ± 17.36 mm2 in normal individuals and 61.77 ± 13.74 mm2 in the GHO group. The mean GHJCT was 2.06 ± 0.35 mm in normal individuals and 1.50 ± 0.28 mm in the GHO group. GHO patients had significantly lower GHJCCSA (P < .001) and GHJCT (P < .001) than normal individuals. Receiver operator characteristics curve analysis revealed that the optimal cutoff score of the GHJCCSA was 82.21 mm2, with a sensitivity of 97.0%, a specificity of 97.0%, and an area under the curve of 0.99 (95% CI: 0.97-1.00). Although GHJCCSA and GHJCT were both significantly associated with GHO, the GHJCCSA was a more sensitive measurement parameter.

Time-Dependent Change in Cartilage Repair Tissue Evaluated by Magnetic Resonance Imaging up to 2 years after Atelocollagen-Assisted Autologous Cartilage Transplantation: Data from the CaTCh Study.

ObjectiveTo elucidate the time course of magnetic resonance imaging (MRI)–based morphological and qualitative outcomes after an atelocollagen-assisted autologous chondrocyte implantation (ACI) and to analyze the correlation between arthroscopic and MRI-based assessment.DesignWe included ACI recipients from a multicenter registration study (CaTCh [Cartilage Treatment in Chiba] study). Morphological (3-dimensional magnetic resonance observation of cartilage repair tissue: 3D-MOCART, MOCART2.0) and qualitative assessment (T2- and T1rho-mapping) by MRI were conducted at 6, 12, and 24 months post-implantation. Global T2 and T1rho indices (T2 and T1rho in repair tissue divided by T2 and T1rho in normal cartilage) were calculated. Arthroscopic second-look assessment was performed in 4 and 15 knees at 12 and 24 months post-implantation, respectively.ResultsThe 3D-MOCART over 12 months witnessed significant patient improvement, but some presented subchondral bone degeneration as early as 6 months. The MOCART2.0 improved from 57.5 to 71.3 between 6 and 24 months (P = 0.02). The global T2 index decreased from 1.7 to 1.2 between 6 and 24 months (P < 0.001). The global T1rho index decreased from 1.5 to 1.3 between 6 and 24 months (P = 0.004). Normal or nearly normal ICRS-CRA (cartilage repair assessment scale developed by the International Cartilage Repair Society) grades were achieved in 86% and 93% of the lesions at 12 and 24 months, respectively. Better ICRS-CRA grade corresponded to better MOCART2.0, with no trend in the T2 and T1rho values.ConclusionsAtelocollagen-assisted ACI improved the MRI-based morphological and qualitative outcomes until 24 months post-surgery, and normal or nearly normal grades were achieved in most lesions by arthroscopic assessment. MRI assessment may be an alternative to arthroscopic assessment.

Benefits and Mechanisms of Exercise Training for Knee Osteoarthritis

Knee osteoarthritis is a chronic degenerative disease. Cartilage and subchondral bone degeneration, as well as synovitis, are the main pathological changes associated with knee osteoarthritis. Mechanical overload, inflammation, metabolic factors, hormonal changes, and aging play a vital role in aggravating the progression of knee osteoarthritis. The main treatments for knee osteoarthritis include pharmacotherapy, physiotherapy, and surgery. However, pharmacotherapy has many side effects, and surgery is only suitable for patients with end-stage knee osteoarthritis. Exercise training, as a complementary and adjunctive physiotherapy, can prevent cartilage degeneration, inhibit inflammation, and prevent loss of the subchondral bone and metaphyseal bone trabeculae. Increasing evidence indicates that exercise training can improve pain, stiffness, joint dysfunction, and muscle weakness in patients with knee osteoarthritis. There are several exercise trainings options for the treatment of knee osteoarthritis, including aerobic exercise, strength training, neuromuscular exercise, balance training, proprioception training, aquatic exercise, and traditional exercise. For Knee osteoarthritis (KOA) experimental animals, those exercise trainings can reduce inflammation, delay cartilage and bone degeneration, change tendon, and muscle structure. In this review, we summarize the main symptoms of knee osteoarthritis, the mechanisms of exercise training, and the therapeutic effects of different exercise training methods on patients with knee osteoarthritis. We hope this review will allow patients in different situations to receive appropriate exercise therapy for knee osteoarthritis, and provide a reference for further research and clinical application of exercise training for knee osteoarthritis.

The expression of Netrin-1 in the MIA-induced osteoarthritic temporomandibular joint in mice

Subchondral bone degeneration is the main pathological change during temporomandibular joint (TMJ) osteoarthritis (OA) development. Netrin-1, an axon-guiding factor, might play roles in OA development and pain. The purpose of this study was to investigate the expression of Netrin-1 in TMJ OA and its possible role in the progression of TMJ OA and pain. The synovial fluids of temporomandibular joint disorders (TMDs) patients were collected for Netrin-1 by enzyme linked immunosorbent assay (ELISA). TMJ OA model was built by MIA joint injection, and then the von Frey test, hematoxylin & eosin (H&E) staining, toluidine blue (TB) staining, immunohistochemical (IHC) staining and micro-CT were performed. After induction of osteoclast differentiation of raw264.7 cells, immunofluorescence (IF) was used to detect the Netrin-1 and its receptors on osteoclast membrane. The concentration of Netrin-1 increased in the synovial fluid of TMJ OA patients. After MIA injection to TMJ, the head withdrawal threshold (HWT) was significantly decreased. Microscopically, the structural disorder of subchondral bone was the most obvious at the 2nd week after MIA injection. In addition, Netrin-1 expression increased in the subchondral bone at the 2nd week after MIA injection. In vitro, the expressions of Netrin-1 and its receptor Unc5B were upregulated on the osteoclast membrane. Netrin-1 might be an important regulator during bone degeneration and pain in the process of TMJ OA.

Optimally dosed nanoceria attenuates osteoarthritic degeneration of joint cartilage and subchondral bone

• Nanoceria injection to inflamed TMJ rescued the degeneration cartilage and subchondyle bone in vivo . • Anti-apoptotic and anti-inflammatory actions of nanoceria were proven to be the major molecular mechanisms. • Nanoceria is considered a nanotherapeutic candidate for the local treatment of degenerative joint diseases. Osteoarthritis entails excessive ROS generation, severe inflammatory responses, and anatomical destruction of cartilage and subchondral bone. Nanoceria holds antioxidant activity, exerting therapeutic efficacy under high ROS conditions. Here we investigate if the nanoceria properly administered to an osteoarthritic joint would be effective in protecting the cartilage and bone against osteoarthritic degeneration. Three-days post-induction of osteoarthritis in a rat temporomandibular joint, nanoceria (~20 nm) at varying doses (100 ~ 2000 µg/mL) were locally administered once, and tissue samples were analyzed at 10 days post-treatment. The nanoceria-administered groups could preserve the cartilage and subchondral anatomical structure of joint; particularly at 500 µg/mL, the preservation of quantitated hypertrophic layer and cartilage proteoglycan was as high as ~ 80% ( vs . ~ 30% in an osteoarthritic group), albeit higher doses gradually shielded the efficacy (~50–60%). The degeneration of subchondral bone was thus significantly prevented by the nanoceria treatment; ~70–80% of intact control with 500 µg/mL vs. ~ 50% in the osteoarthritic group. Moreover, the nanoceria treatment profoundly reduced the degenerative symptoms including cellular apoptosis and the secretion of catabolic proteins (COX2/PGE2) and pro-inflammatory cytokines (IL-1β/TNFα) while boosting regenerative events such as the polarization of M2 macrophages (CD206/163) and the production of anti-inflammatory cytokines (IL-10) and chondrogenic glycoproteins. The excessive ROS generated in the osteoarthritis joint was observed to be effectively scavenged by the nanoceria. Such therapeutic effects of nanoceria witnessed in vivo were further demonstrated in parallel with the in vitro experiments particularly involving the osteoarthritis-mimicking chondrocytes/macrophages co-culture models, where the anti-apoptotic and immunomodulatory roles of nanoceria were revealed to be major molecular mechanisms. The present findings may place the nanoceria a promising nanotherapeutic candidate for the treatment of degenerative joint diseases.

Diabetes mellitus accelerates the progression of osteoarthritis in streptozotocin-induced diabetic mice by deteriorating bone microarchitecture, bone mineral composition, and bone strength of subchondral bone.

BackgroundThe purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced.MethodsMice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties.ResultsGlycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone specific alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups.ConclusionsThe glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.

Differences in the progression of articular cartilage and subchondral bone degeneration between two mouse models

Purpose: Osteoarthritis (OA) of the knee is a common cause of chronic pain and restriction in performing activities of daily living. Whether OA arises from articular cartilage degeneration or subchondral bone degeneration remains unclear. Currently, the anterior cruciate ligament transection (ACL-T) model and the destabilization of the medial meniscus (DMM) model are used as animal models of OA. Studies have shown that OA progresses more slowly in the DMM model than in the ACL-T model. There are few reports directly comparing the two models and no consensus exists about the mechanism of OA in the two models.

Thermogravimetric analysis of cancellous bone of humerus head in patients undergoing total shoulder arthroplasty

Prior to shoulder replacement, the quality of cancellous bone stock of humerus head should be evaluated. Thermogravimetric analysis (TGA) has already been utilized to assess thermal stability of cancellous bone mineral, collected from the femoral head of patients with osteoarthritis and osteoporosis. Our workgroup has recently examined the thermal parameters of rotator cuff of patients undergoing reversed shoulder replacement. We hypothesized that TGA of humerus head would indicate difference in the bone quality of orthopedic and trauma patients. We also hypothesized that the calorimetric data could correlate with the grade of degenerative changes. Cylindrical subchondral humeral head samples were collected from patients subjected to reversed shoulder replacement due to orthopedic or trauma indications. Then, calorimetric parameters were measured using DTA/TG analysis. Radiological evaluation was also performed to classify the grade of osteoarthritis. In case of orthopedic samples, the calorimetric parameters indicated a moderate to severe degree of bone damage and loss of mineralization, because of the progressed osteoarthritis. Meanwhile, the trauma samples exhibited only moderate or minimal subchondral bone degeneration. DTA curves showed different patterns and indicated shifts in transition temperatures, comparing control and pathologic samples. In addition, correlation was found between the degree of osteoarthritis and calorimetric enthalpy. DTA/TG analysis of humerus head samples indicated marked differences in bone quality of orthopedic and trauma patients. Further investigation is needed to differentiate the calorimetric parameters of different layers of subchondral bone.

CB2 agonism controls pain and subchondral bone degeneration induced by mono-iodoacetate: Implications GPCR functional bias and tolerance development

Background and purposeThe endocannabinoid system became a promising target for osteoarthritis (OA) treatment. Functional selectivity of cannabinoids may increase their beneficial properties while reducing side effects. The aim of the present study was to evaluate the analgesic potential of two functionally biased CB2 agonists in different treatment regimens to propose the best pharmacological approach for OA management. Experimental approachTwo functionally selective CB2 agonists were administered i.p. – JWH133 (cAMP biased) and GW833972A (β-arrestin biased), in a chemically induced model of OA in rats. The drugs were tested in acute and chronic treatment regimens. Analgesic effects were assessed by pressure application measurement and kinetic weight bearing. X-ray microtomography was used for the morphometric analysis of the femur’s subchondral bone tissue. Underlying biochemical changes were analysed via RT-qPCR. Key resultsDose-response studies established the effective dose for both JWH133 and GW833972A. In chronic treatment paradigms, JWH133 was able to elicit analgesia throughout the course of the experiment, whereas GW833972A lost its efficacy after 2 days of treatment. Later studies revealed improvement in subchondral bone architecture and decrement of matrix metalloproteinases and proinflammatory factors expression following JWH133 chronic treatment. Conclusion and implicationsData presents analgesic and disease-modifying potential of CB2 agonists in OA treatment. Moreover, the study revealed more pronounced tolerance development for analgesic effects of the β-arrestin biased CB2 agonist GW833972A. These results provide a better understanding of the molecular underpinnings of the anti-nociceptive potential of CB2 agonists and may improve drug development processes for any cannabinoid-based chronic pain therapy.

Overexpression of MMPs, cytokines, and RANKL/OPG in temporomandibular joint osteoarthritis and their association with joint pain, mouth opening, and bone degeneration: A preliminary report.

This study aimed to determine the expression of distinct matrix metalloproteinases, cytokines, and bone resorptive factors in temporomandibular joint osteoarthritis (TMJ-OA) patients and their association with joint pain, mouth opening, and subchondral bone degeneration. Twelve patients affected with TMJ-OA (n=5), disk displacement without reduction (DDWoR) (n=3), or disk displacement with reduction (DDWR) (n=4) were selected. Joint pain was quantified by using visual analog scale, mouth opening was quantified at the maximum pain-free aperture, and bone degeneration was quantified using joint imaging. Synovial fluid samples were collected and immediately processed for cell and synovial fluid recovering. From cells, the MMP-1, MMP-2, MMP-8, MMP-13, IL-6, IL-23, and TNF-α expression was quantified by qPCR. From synovial fluid, the RANKL and OPG levels were quantified by ELISA. Higher levels of MMP-1, MMP-8, MMP-13, IL-6, IL-23, TNF-α, and RANKL/OPG ratio were detected in TMJ-OA compared with DDWoR and DDWR patients (p<.05). Joint pain significantly correlated with TNF-α levels (r=.975, p=.029). Besides, imaging signs of bone degeneration significantly correlated with RANKL/OPG ratio (r=.949, p=.042). Conversely, mouth opening did not correlate with any of the analyzed mediators. During TMJ-OA, a pathological response characterized by the overexpression of TNF-α and RANKL/OPG could be involved in joint pain and subchondral bone degeneration.

Self-assembled artificial cartilage-hydroxyapatite conjugate for combined articular cartilage and subchondral bone repair

Self-assembled artificial cartilage-hydroxyapatite conjugate for combined articular cartilage and subchondral bone repair

A novel, self-assembled artificial cartilage-hydroxyapatite conjugate for combined articular cartilage and subchondral bone repair: histopathological analysis of cartilage tissue engineering in rat knee joints.

PurposeWe previously created a self-assembled cartilage-like complex in vitro from only three cartilage components, hyaluronic acid (HA), aggrecan (AG) and type II collagen, without other materials such as cross-linking agents. Based on this self-organized AG/HA/collagen complex, we have created three novel types of biphasic cartilage and bone-like scaffolds combined with hydroxyapatite (HAP) for osteochondral tissue engineering. These scaffolds have been developed from self-assembled cartilage component molecules and HAP at the nanometer scale by manipulating the intermolecular relations.Patients and methodsThe surface structure of each self-organized biphasic cartilage and bone-like scaffold was evaluated by scanning electron microscopy, whereas the viscoelasticity was also analyzed in vitro. Three types of artificial cartilage–HAP conjugates were implanted into an osteochondral defect in rat knee joints, and bone and cartilage tissues of the implanted site were examined 4 and 8 weeks after implantation. The tissues were examined histopathologically to evaluate the effects of the implantation on the articular cartilage and subchondral bone tissues.ResultsOur in vitro and in vivo data reveal that the self-organized biphasic cartilage and bone-like scaffold conjugated with HAP are superior to the scaffold with no HAP in both cartilage regeneration and subchondral bone regeneration.ConclusionOur present study indicates that the self-organized biphasic cartilage and bone-like scaffold, which is conjugated with an HAP layer, may have potential not only to repair articular cartilage defects but also to ameliorate the degeneration of subchondral bone in the diseases with osteochondral defect.