Subchondral Bone Microstructure Research Articles

Effects of alendronate on cartilage lesions and micro-architecture deterioration of subchondral bone in patellofemoral osteoarthritic ovariectomized rats with patella-baja

BackgroundPatellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks.MethodsPatella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague–Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 μg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT).ResultsOur results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone.ConclusionThe early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice

Background: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression. Purpose: To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice. Study Design: Controlled laboratory study. Methods: OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro−computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically. Results: Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed. Conclusion: Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery. Clinical Relevance: TXA might be beneficial in patients with posttraumatic OA of the knee.

The CREB1 inhibitor 666-15 maintains cartilage homeostasis and mitigates osteoarthritis progression.

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). CREB1 was hyperactive in osteoarthritic articular cartilage, interleukin (IL)-1β-treated cartilage explants, and IL-1β- or carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-treated chondrocytes. 666-15 enhanced cell viability of OA-like chondrocytes and alleviated IL-1β- or CCCP-induced chondrocyte injury through inhibition of mitochondrial dysfunction-associated apoptosis. Moreover, inhibition of CREB1 by 666-15 suppressed expression of ADAMTS4. Additionally, 666-15 alleviated joint degeneration in an ACLT mouse model. Hyperactive CREB1 played a critical role in OA development, and 666-15 exerted anti-IL-1β or anti-CCCP effects in vitro as well as joint-protective effects in vivo. 666-15 may therefore be used as a promising anti-OA drug.

Total Glucosides of Peony Alleviate Joint Destruction in Rabbits With Osteoarthritis

Objective Although many painkillers can be used to relieve the symptoms of osteoarthritis (OA), these drugs do not address joint bone degeneration and muscle wasting, highlighting the need for alternative treatments. This study evaluated the ability of various plant extracts to inhibit joint destruction, focusing on the total glucosides of peony (TGP) obtained from the normal Chinese medication white peony. Methods A rabbit OA model was established by anterior cruciate ligament resection (ACLT) and TGP treatment was initiated for 3 months. The morphologies of the skeletal muscle fibers, articular cartilage, and subchondral bone of the knee joint were histologically observed via X-ray and micro-computed tomography scan. Results TGP significantly reduced the histopathological changes associated with skeletal muscle atrophy and inflammation, and alleviated cartilage degeneration. In addition, TGP treatment significantly improved the bone density and microstructure of subchondral bone in rabbit knee joints compared with the model group. Conclusion The results suggested that TGP treatment may alleviate the progression of osteoarthritis and reduce the destruction of joint cartilage and bone in ACLT.

Characterization and Advancement of an Evaluation Method for the Treatment of Spontaneous Osteoarthritis in STR/ort Mice: GRGDS Peptides as a Potential Treatment for Osteoarthritis

STR/ort mice spontaneously exhibit the typical osteoarthritis (OA) phenotype. However, studies describing the relationship between cartilage histology, epiphyseal trabecular bone, and age are lacking. We aimed to evaluate the typical OA markers and quantify the subchondral bone trabecular parameters in STR/ort male mice at different weeks of age. We then developed an evaluation model for OA treatment. We graded the knee cartilage damage using the Osteoarthritis Research Society International (OARSI) score in STR/ort male mice with or without GRGDS treatment. We measured the levels of typical OA markers, including aggrecan fragments, matrix metallopeptidase-13 (MMP-13), collagen type X alpha 1 chain (COL10A1), and SRY-box transcription factor 9 (Sox9), and quantified epiphyseal trabecular parameters. Compared to the young age group, elderly mice showed an increased OARSI score, decreased chondrocyte columns of the growth plate, elevated expression of OA markers (aggrecan fragments, MMP13, and COL10A1), and decreased expression of Sox9 at the articular cartilage region in elderly STR/ort mice. Aging also significantly enhanced the subchondral bone remodeling and microstructure change in the tibial plateau. Moreover, GRGDS treatment mitigated these subchondral abnormalities. Our study presents suitable evaluation methods to characterize and measure the efficacy of cartilage damage treatments in STR/ort mice with spontaneous OA.

The effect of postmenopausal osteoporosis on subchondral bone pathology in a rat model of knee osteoarthritis

This study aimed to investigate the additional effect of ovariectomy-induced osteoporosis (OP) on the pathology of knee osteoarthritis (OA) in a rat meniscectomized model, particularly focusing on subchondral bone changes and pain behaviour. Rats were divided into four groups, sham, OP, OA, OP plus OA, and assessed for histology, osteoclast activity, subchondral bone microstructure, and pain-related behaviour. Rats with OP plus OA had significantly increased calcified cartilage and subchondral bone damage scores, increased densities of subchondral osteoclasts in the weight-bearing area, and more porous subchondral trabecular bone compared with rats with OA. Loss of tidemark integrity was observed most frequently in rats with OP plus OA. The density of subchondral osteoclasts correlated with the calcified cartilage and subchondral bone damage score in rats with OA (OA and OP plus OA). No significant differences in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) expression ratio in subchondral bone and pain-related behavioural tests were observed between rats with OA and rats with OP plus OA. In rats with OA, coexisting OP potentially aggravated OA pathology mainly in calcified cartilage and subchondral trabecular bone by increasing subchondral osteoclast activity.

Microstructural adaptations of the subchondral bone are related to the mechanical axis deviation in end stage varus oa knees.

Recent studies highlighted the crucial contribution of subchondral bone to OA development. Yet, only limited data have been reported on the relation between alteration to cartilage morphology, structural properties of the subchondral bone plate (SBP) and underlying subchondral trabecular bone (STB). Furthermore, the relationship between the morphometry of the cartilage and bone in the tibial plateau and the OA-induced changes in the joint's mechanical axis remains unexplored. Therefore, a visualisation and quantification of cartilage and subchondral bone microstructure in the medial tibial plateau was performed. End stage knee-OA patients with varus alignment and scheduled for total knee arthroplasty (TKA) underwent preoperative fulllength radiography to measure the hip-knee-ankle angle (HKA) and the mechanical-axis deviation (MAD). 18 tibial plateaux were μ-CT scanned (20.1 μm/voxel). Cartilage thickness, SBP, and STB microarchitecture were quantified in 10 volumes of interest (VOIs) in each medial tibial plateau. Significant differences (p < 0.001) were found for cartilage thickness, SBP, and STB microarchitecture parameters among the VOIs. Closer to the mechanical axis, cartilage thickness was consistently smaller, while SBP thickness and STB bone volume fraction (BV/TV) were higher. Moreover, trabeculae were also more superior-inferiorly oriented, i.e. perpendicular to the transverse plane of the tibial plateau. As cartilage and subchondral bone changes reflect responses to local mechanical loading patterns in the joint, the results suggested that region-specific subchondral bone adaptations were related to the degree of varus deformity. More specifically, subchondral sclerosis appeared to be most pronounced closer to the mechanical axis of the knee.

Early zoledronate treatment inhibits subchondral bone microstructural changes in skeletally-mature, ACL-transected canine knees.

Anterior cruciate ligament (ACL) tear leads to post-traumatic osteoarthritis (PTOA), a significant clinical burden worldwide that currently has no cure. Recent studies suggest a role of subchondral bone adaptations in the development of PTOA. Particularly, microstructural changes in the rod-and-plate microstructure of subchondral bone may precede and contribute to OA progression. In this study, we quantified microstructural changes in subchondral trabecular rods and plates after ACL-transection for the first time in the well-established preclinical canine model of PTOA and investigated the therapeutic potentials of a bisphosphonate (zoledronate) and NSAID treatment (meloxicam). Unilateral hindlimb ACL transection was performed on skeletally-mature (2-year-old, N = 20) and juvenile (10-month-old, N = 20) male beagles. Animals were assigned to 4 groups (N = 5): ACLT, un-operated control, ACLT with zoledronate, and ACLT with meloxicam treatment. Subchondral bone microstructure was evaluated by micro-computed tomography and cartilage integrity was evaluated histologically. We found that ACL-induced subchondral bone changes depended on skeletal maturity of animals. In mature animals, significant loss of trabecular plates that resulted in reduced PR ratio occurred at Month 1 and persisted until Month 8. Zoledronate treatment prevented trabecular plate loss while meloxicam treatment did not. Whether cartilage degeneration is also attenuated warrants further investigation. In juvenile animals that have not reached skeletal maturity, transient changes in trabecular plate and rod microstructure occurred at Month 3 but not Month 9. Neither zoledronate nor meloxicam treatment attenuated bone microstructural changes or cartilage damages. Findings from this study suggest that early inhibition of bone resorption by bisphosphonate after injury may be a promising therapeutic approach to prevent alterations in subchondral bone microstructure associated with PTOA. Our results further demonstrate that pathogenesis of PTOA may differ between adolescent and adult patients and therefore require distinct management strategies.

Open-source pipeline for automatic segmentation and microstructural analysis of murine knee subchondral bone.

A segmented dataset of μCT scans from 62 knees (healthy and arthritic) from 10-week male C57BL/6 mice was used to train a U-Net type architecture to automate segmentation of the subchondral trabecular bone. These segmentations were used in tandem with the original scans as input for microstructural analysis along with thresholded trabecular bone. Manually and U-Net segmented ROIs were fed into two available pipelines for microstructural analysis: the ITKBoneMorphometry library and CTan (SKYSCAN). Outcome parameters were compared between pipelines, including: bone volume (BV), total volume (TV), BV/TV, trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp), and bone surface density (BSBV). There was good agreement for all bone measures comparing the manual and U-Net pipelines utilizing ITK (R = 0.88-0.98) and CTAn (R = 0.91-0.98). ITK and CTAn showed good agreement for BV, TV, BV/TV, TbTh and BSBV (R = 0.9-0.98). However, limited agreement was seen between TbN (R = 0.73) and TbSb (R = 0.59) due to methodological differences in how spacing is evaluated. Microstructural parameters generated from manual and automatic segmentations showed high correlation across all measures. Using the CTAn pipeline yielded strong R2 values (0.83-0.96) and very strong agreement based on ICC (0.90-0.98). The ITK pipeline yielded similarly high R2 values (0.91-0.96, except for TbN (0.77)), and ICC values (0.88-0.98). The automated segmentations yield lower average values for BV, TV and BV/TV (ranging from 14 % to 6.3 %), but differences were not found to be influenced by the mean ROI values. This integrated pipeline seamlessly automated both segmentation and quantification of the proximal tibia subchondral bone microstructure. This automated pipeline allows the analysis of large volumes of data, and its open-source nature may enable the standardization of microstructural analysis of trabecular bone across different research groups.

280 mT static magnetic field promotes the growth of postpartum condylar cartilage

ABSTRACT Purpose Functional appliances made of permanent magnets have been used in jaw orthopedic treatment. However, whether the static magnetic field (SMF) generated by permanent magnets promotes the developmental sequence of condylar cartilage and thus promotes the growth of the mandible remains to be studied. The aim of this study was to investigate the effects of 280 mT SMF on postnatal condylar chondrogenesis and endochondral ossification and the roles of FLRT3, FGF2 and BMP2 signaling in this chondrodevelopmental sequences. Methods Forty-eight rats were assigned to two groups (control and SMF). The condyles were collected at the specified time points. The histomorphological changes in the condyle were observed by histological staining. The expression of proteins related to the proliferation and differentiation of the condylar cartilage and the changes in subchondral bone microstructure were analyzed by immunohistochemical staining and micro-CT scanning. FLRT3, FGF2, and BMP2 expression was detected by immunofluorescence staining. Results Under SMF stimulation, the cartilage of young rats grew longitudinally and laterally, and the thickness of the cartilage became thinner as it grew. The SMF promoted the proliferation and differentiation of condylar chondrocytes and endochondral ossification and increased subchondral bone mineral density, and BMP2 signaling was involved. Moreover, under SMF loading, the increased expression of FGF2 and FLRT3 were involved in regulating cartilage morphogenesis and growth. In late development, the decreased expression of FGF2/FLRT3 and the increased expression of BMP2 promoted endochondral ossification. The SMF accelerated this opposite expression trend. Conclusion FGF2/FLRT3 and BMP2 signals are involved in the regulatory effect of SMF exposure on chondrogenesis and endochondral ossification, which provides a theoretical basis for the clinical use of magnetic appliances to promote condylar growth.

Increased joint loading induces subchondral bone loss of the temporomandibular joint via the RANTES-CCRs-Akt2 axis.

Early-stage temporomandibular joint osteoarthritis (TMJOA) is characterized by excessive subchondral bone loss. Emerging evidence suggests that TMJ disc displacement is involved, but the pathogenic mechanism remains unclear. Here, we established a rat model of TMJOA that simulated disc displacement with a capacitance-based force-sensing system to directly measure articular surface pressure in vivo. Micro-CT, histological staining, immunofluorescence staining, IHC staining, and Western blot were used to assess pathological changes and underlying mechanisms of TMJOA in the rat model in vivo as well as in RAW264.7 cells in vitro. We found that disc displacement led to significantly higher pressure on the articular surface, which caused rapid subchondral bone loss via activation of the RANTES-chemokine receptors-Akt2 (RANTES-CCRs-Akt2) axis. Inhibition of RANTES or Akt2 attenuated subchondral bone loss and resulted in improved subchondral bone microstructure. Cytological studies substantiated that RANTES regulated osteoclast formation by binding to its receptor CCRs and activating the Akt2 pathway. The clinical evidence further supported that RANTES was a potential biomarker for predicting subchondral bone loss in early-stage TMJOA. Taken together, this study demonstrates important functions of the RANTES-CCRs-Akt2 axis in the regulation of subchondral bone remodeling and provides further knowledge of how disc displacement causes TMJOA.

Investigating the subchondral trabecular bone microstructure in patients with osteonecrosis of the femoral head using multi-detector row computed tomography.

To analyse the microstructural changes of subchondral trabecular bone in patients with osteonecrosis of the femoral head (ONFH) using multi-detector row computed tomography (MDCT). We retrospectively investigated 76 hips in 50 patients diagnosed with ONFH between 2017 and 2021. Groups 1, 2, 3, and 4 comprised hips without ONFH, ONFH without femoral head collapse (FHC), ONFH with mild collapse (<2 mm), and ONFH with severe collapse (>2 mm), respectively. All patients underwent MDCT, and the subchondral trabecular bone microstructure was assessed. Regions of interests were set at the lateral boundary of the femoral head necrotic lesion and centre of the acetabular weight-bearing portion. In both the femoral head and the acetabular regions, there were significant differences in Groups 2 and 3 compared to Group 1, with increased volumetric bone mineral density and apparent bone volume fraction, and more plate-like with increased connectivity, indicating that osteosclerotic changes were occurring. In both the femoral head and the acetabular regions, osteosclerotic changes of subchondral trabecular bone microstructure were present before FHC.

Scutellarin ameliorates osteoarthritis by protecting chondrocytes and subchondral bone microstructure by inactivating NF-κB/MAPK signal transduction

Osteoarthritis (OA), a chronic degenerative disease, is a major cause of pain, disability, and reduced quality of life among the elderly worldwide. The key to treating it is early prevention and effective intervention. The anti-inflammatory effects of scutellarin (SCU), a flavonoid derived from Erigeron breviscapus, have been increasingly reported. However, the mechanism by which SCU affects OA remains unclear. This study aimed to investigate the therapeutic effects and potential molecular mechanisms of SCU in the development of OA. Here, we found that SCU inhibited interleukin (IL)− 1β-induced degradation of the extracellular matrix (ECM) of cartilage through the NF-kappaB/mitogen-activated protein kinases (NF-κB/MAPK) signaling pathway. In addition, in vivo data showed that SCU significantly reduced cartilage damage in the destabilization of the medial meniscus (DMM) mouse model and ovariectomy (OVX)-induced subchondral bone loss and cartilage degeneration in mice. In summary, our data showed that SCU is expected to become a potentially effective candidate treatment strategy for OA.

Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis.

The monosodium iodoacetate (MIA)-induced osteoarthritis (OA) may lead to cartilage degeneration and histopathological lesions. However, the correlation between inflammatory reaction and subchondral bone remodeling in a rodent osteoarthritic model is ambiguous. In this study, intra-articular injection of MIA was performed in 36 four-week-old specific pathogen-free male Wistar rats to induce OA. After 4 weeks of intervention, changes in intrinsic structural properties of the subchondral bones were measured, and the histological evaluation, as well as biochemical analysis, was conducted. We found that intra-articular injection of MIA increased chondrocyte apoptosis and promoted cartilage matrix degradation, such as cartilage surface defects and shallow or disappearing staining. MIA also induced inflammation, improved the expression of IL-1β, TNF-α, and matrix metalloproteinase, and decreased the expression of cartilage-specific proteins with the extension of modeling time. Meanwhile, the MIA also significantly accelerated the subchondral bone remodeling, as shown by the decreased subchondral bone density, thinning of trabeculae, disordered cartilage structure, and morphology. In conclusion, we have shown that MIA-induced rodent osteoarthritic model would cause decreased subchondral bone density, sparse trabecular bone, and other manifestations of osteoporosis accompanied by an inflammatory response, which would worsen with the progression of modeling time. Our results suggest that different phases of MIA-induced OA are associated with the changes in subchondral bone microstructure and the progression of local inflammation.

Quantifying the Human Subchondral Trabecular Bone Microstructure in Osteoarthritis with Clinical CT.

Osteoarthritis (OA) is characterized by critical alterations of the subchondral bone microstructure, besides the well‐known cartilaginous changes. Clinical computed tomography (CT) detection of quantitative 3D microstructural subchondral bone parameters is applied to monitor changes of subchondral bone structure in different stages of human OA and is compared with micro‐CT, the gold standard. Determination by clinical CT (287 µm resolution) of key microstructural parameters in tibial plateaus with mild‐to‐moderate and severe OA reveals strong correlations to micro‐CT (35 µm), high inter‐ and intraobserver reliability, and small relative differences. In vivo, normal, mild‐to‐moderate, and severe OA are compared with clinical CT (331 µm). All approaches detect characteristic expanded trabecular structure in severe OA and fundamental microstructural correlations with clinical OA stage. Multivariate analyses at various in vivo and ex vivo imaging resolutions always reliably separate mild‐to‐moderate from severe OA (except mild‐to‐moderate OA from normal), revealing a striking similarity between 287 µm clinical and 35 µm micro‐CT. Thus, accurate structural measurements using clinical CT with a resolution near the trabecular dimensions are possible. Clinical CT offers an opportunity to quantitatively monitor subchondral bone microstructure in clinical and experimental settings as an advanced tool of investigating OA and other diseases affecting bone architecture.

Subchondral involvement in osteonecrosis of the femoral head: insight on local composition, microstructure and vascularization

To determine changes of subchondral bone composition, micro-structure, bone marrow adiposity and micro-vascular perfusion in end-stage osteonecrosis of the femoral head (ONFH) compared to osteoarthritis (OA) using a combined in vivo and ex vivo approach. Male patients up to 70 years old referred for total hip replacement surgery for end-stage ONFH were included (n=14). Fifteen patients with OA were controls. Pre-operative MRI was used to assess bone perfusion (dynamic contrast-enhanced (DCE) sequences) and marrow fat content (chemical shift imaging). Three distinct zones of femoral head subchondral bone - necrotic, sclerotic, distant - were compared between groups. After surgery, plugs were sampled in these zones and Raman spectroscopy was applied to characterize bone mineral and organic components (old and newly-formed), and contrast-enhanced micro-computed tomography (CE-μCT) to determine bone micro-structural parameters and volume of bone marrow adipocytes, using conventional 2D histology as a reference. In the necrotic zone of ONFH patients compared to OA patients: 1) the subchondral plate did not exhibit significant changes in composition nor structure; 2) the volume fraction of subchondral trabecular bone was significantly lower; 3) type-B carbonate substitution was less pronounced, 4) collagen maturity was more pronounced; and 5) bone marrow adipocytes were significantly depleted. The sclerotic zone from the ONFH group showed greater trabecular thickness, and higher DCE-MRI AUC and Ktrans. Volume fraction of subchondral bone, trabecular number, and Kep were significantly lower in the distant zone of the ONFH group. This study demonstrated alterations of subchondral bone microstructure, composition, perfusion and/or adipose content in all zones of the femoral head.

Spatial links between subchondral bone architectural features and cartilage degeneration in osteoarthritic joints

Early diagnosis of osteoarthritis (OA), before the onset of irreversible changes is crucial for understanding the disease process and identifying potential disease-modifying treatments from the earliest stage. OA is a whole joint disease and affects both cartilage and the underlying subchondral bone. However, spatial relationships between cartilage lesion severity (CLS) and microstructural changes in subchondral plate and trabecular bone remain elusive. Herein, we collected femoral heads from hip arthroplasty for primary osteoarthritis (n = 7) and femoral neck fracture (n = 6; non-OA controls) cases. Samples were regionally assessed for cartilage lesions by visual inspection using Outerbridge classification and entire femoral heads were micro-CT scanned. Scans of each femoral head were divided into 4 quadrants followed by morphometric analysis of subchondral plate and trabecular bone in each quadrant. Principal component analysis (PCA), a data reduction method, was employed to assess differences between OA and non-OA samples, and spatial relationship between CLS and subchondral bone changes. Mapping of the trabecular bone microstructure in OA patients with low CLS revealed trabecular organisation resembling non-OA patients, whereas clear differences were identifiable in subchondral plate architecture. The OA-related changes in subchondral plate architecture were summarised in the first principle component (PC1) which correlated with CLS in all quadrants, whilst by comparison such associations in trabecular bone were most prominent in the higher weight-bearing regions of the femoral head. Greater articular cartilage deterioration in OA was regionally-linked with lower BV/TV, TMD and thickness, and greater BS/BV and porosity in the subchondral plate; and with thinner, less separated trabeculae with greater TMD and BS/BV in the trabecular bone. Our findings suggest that impairment of subchondral bone microstructure in early stage of OA is more readily discernible in the cortical plate and that morphological characterisation of the femoral head bone microstructure may allow for earlier OA diagnosis and monitoring of progression.

Parathyroid Hormone (1-34) Attenuates Cartilage Degradation and Preserves Subchondral Bone Micro-architecture in Rats with Patella Baja-Induced-Patellofemoral Joint Osteoarthritis.

Several studies have revealed that PTH1-34 may possess the potential for treating osteoarthritis (OA) and osteoporosis. However, no study has yet determined whether PTH1-34 can be used for the treatment of patella baja-induced patellofemoral joint OA (PFJOA). Thus, this study sought to assess the efficacy of PTH1-34 for the treatment of PFJOA in a rat model. Patella baja was induced in 3-month-old female Sprague-Dawley (SD) rats by patellar ligament shortening (PLS), after which the rats were randomly divided into three groups (n = 12): Sham, PLS, and PTH group (PTH + PLS, PTH1-34, 30µg/kg/d, 5days per week for 10weeks). Thereafter, radiographic imaging, macroscopic and microscopic analyses, immunohistochemistry, and microcomputed tomography (CT) analysis were performed. The appearance of PLS-induced PFJOA promoted obvious changes in the patellar position and structure in the PLS group, which were characterized by cartilage degeneration, subchondral bone microstructure deterioration, patella baja, and increasing patella length. However, these negative characteristics were markedly ameliorated by PTH1-34, which not only inhibited cartilage catabolism by decreasing MMP-13 and ADAMTS-4 but also enhanced anabolism by increasing Col-II and Aggrecan. Furthermore, the micro-CT results showed a marked improvement in subchondral bone microarchitecture. The findings presented herein demonstrated that early treatment with PTH1-34 could improve cartilage metabolism and subchondral bone health in this PFJOA model.

Inhibiting Hh Signaling in Gli1+ Osteogenic Progenitors Alleviates TMJOA

The increased prevalence of temporomandibular joint osteoarthritis (TMJOA) in children and adolescents has drawn considerable attention as it may interfere with mandibular condyle growth, resulting in dento-maxillofacial deformities. However, treatments for osteoarthritis have been ineffective at restoring the damaged bone and cartilage structures due to poor understanding of the underlying degenerative mechanism. In this study, we demonstrate that Gli1+ cells residing in the subchondral bone contribute to bone formation and homeostasis in the mandibular condyle, identifying them as osteogenic progenitors in vivo. Furthermore, we show that, in a TMJOA mouse model, derivatives of Gli1+ cells undergo excessive expansion along with increased but uneven distribution of osteogenic differentiation in the subchondral bone, which leads to abnormal subchondral bone remodeling via Hedgehog (Hh) signaling activation and to the development of TMJOA. The selective pharmacological inhibition and specific genetic inhibition of Hh signaling in Gli1+ osteogenic progenitors result in improved subchondral bone microstructure, attenuated local immune inflammatory response in the subchondral bone, and reduced degeneration of the articular cartilage, providing in vivo functional evidence that targeting Hh signaling in Gli1+ osteogenic progenitors can modulate bone homeostasis in osteoarthritis and provide a potential approach for treating TMJOA.

Hemodynamic stress shapes subchondral bone in osteoarthritis: An emerging hypothesis.

Osteoarthritis (OA) is no longer regarded as a simple wear-and-tear problem of articular cartilage. Instead, OA is a whole joint disorder involving both cartilaginous and non-cartilaginous tissues such as subchondral bone and synovium. Among them, subchondral bone undergoes constant remodeling in response to the changes of mechanical environment. Current understanding of subchondral bone disturbance in OA is limited to its link with an altered local mechanical loading as a result of ligament or meniscus injury. Very recently, hypertension, the most common vascular morbidity, has been emerged as an independent risk factor of OA. It might suggest a plausible role of systemic hemodynamic mechanical stress in subchondral bone remodeling and the pathogenesis of OA. However, their relationship remains not fully understood. Based on our preliminary clinical observation on the association of hemodynamic parameters with subchondral bone mass and microstructure in late-stage knee OA patients, we formulate a vascular etiology hypothesis of OA from a mechanobiology perspective. Noteworthily, hemodynamic stress associated with subchondral bone mineral density; yet compressive mechanical loading does not. Furthermore, hemodynamic parameters positively correlated with subchondral plate-like trabecular bone volume but negatively associated with rod-like trabecular bone volume. In contrast, compressive mechanical loading tends to increase both plate-like and rod-like trabecular bone volume. Taken together, it warrants further investigations into the distinct role of hemodynamic or compressive stress in shaping subchondral bone in the pathophysiology of OA.The Translational potential of this articleThis work provides a new insight, from the angle of biomechanics, into the emerging role of vascular pathologies, such as hypertension, in the pathogenesis of OA. It might open up a new avenue for the development of a mechanism-based discovery of novel diagnostics and therapeutics.