scholarly journals Developmental Transformation and Reduction of Connective Cavities within the Subchondral Bone

2019 ◽  
Vol 20 (3) ◽  
pp. 770 ◽  
Author(s):  
Shahed Taheri ◽  
Thomas Winkler ◽  
Lia Schenk ◽  
Carl Neuerburg ◽  
Sebastian Baumbach ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Volume Fraction ◽  
Early Adulthood ◽  
Sample Type ◽  
Bone Volume Fraction ◽  
Medial Condyle ◽  
Calcified Cartilage ◽  
Degree Of Anisotropy ◽  
Early Oa

It is widely accepted that the subchondral bone (SCB) plays a crucial role in the physiopathology of osteoarthritis (OA), although its contribution is still debated. Much of the pre-clinical research on the role of SCB is concentrated on comparative evaluations of healthy vs. early OA or early OA vs. advanced OA cases, while neglecting how pure maturation could change the SCB’s microstructure. To assess the transformations of the healthy SCB from young age to early adulthood, we examined the microstructure and material composition of the medial condyle of the femur in calves (three months) and cattle (18 months) for the calcified cartilage (CC) and the subchondral bone plate (SCBP). The entire subchondral zone (SCZ) was significantly thicker in cattle compared to calves, although the proportion of the CC and SCBP thicknesses were relatively constant. The trabecular number (Tb.N.) and the connectivity density (Conn.D) were significantly higher in the deeper region of the SCZ, while the bone volume fraction (BV/TV), and the degree of anisotropy (DA) were more affected by age rather than the region. The mineralization increased within the first 250 µm of the SCZ irrespective of sample type, and became stable thereafter. Cattle exhibited higher mineralization than calves at all depths, with a mean Ca/P ratio of 1.59 and 1.64 for calves and cattle, respectively. Collectively, these results indicate that the SCZ is highly dynamic at early age, and CC is the most dynamic layer of the SCZ.

scholarly journals Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

2020 ◽  
Author(s):  
Bo Liu ◽  
Chen-Chen Ji ◽  
Yi-Jie Shao ◽  
Ting Liang ◽  
Jia-Heng He ◽  
...  
Keyword(s):  
Elastic Modulus ◽  
Subchondral Bone ◽  
Structural Changes ◽  
Sham Group ◽  
Volume Fraction ◽  
Control Group ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Trabecular Thickness ◽  
Early Oa

Abstract BackgroundEtoricoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor, is commonly used in osteoarthritis (OA) for pain relief. The purpose of our study was to investigate the effects of Etoricoxib on mouse subchondral bone in early OA.MethodsOA was induced via destabilization of the medial meniscus (DMM) in C57BL/6J mice. After surgery, the mice were randomly and equally divided into five groups: a sham-operated control group (Sham group), an osteoarthritis (OA) group (DMM group), an OA treated with Etoricoxib 5mg/kg (DMM+E5) group, an OA treated with Etoricoxib 10mg/kg (DMM+E10) group, and an OA treated with Etoricoxib 20mg/kg (DMM+E20) group. Mice in the Sham group and DMM group were injected with a similar dose of vehicle (40% ethyl alcohol–saline solution). Four weeks after treatment, mice were euthanized. Micro computed tomography (Mirco-CT) analysis, Safranin O-Fast Green staining, hematoxylin and eosin (HE) staining were performed to evaluate morphological and structural changes. In addition, atomic force microscopy (AFM) analysis was performed to evaluate changes in the elastic modulus. Furthermore, changes in microstructure were detected by scanning electron microscopy (SEM).ResultsEtoricoxib inhibited osteophyte formation in the subchondral bone. However, it also reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th), and more microfractures and pores were observed in the subchondral bone. Moreover, Etoricoxib reduced the elastic modulus of subchondral bone. Furthermore, exposure to Etoricoxib further increased the empty/total osteocyte ratio of the subchondral bone. In cartilage and synovium, Etoricoxib did not significantly change the Osteoarthritis Research Society International (OARSI) score, the modified Mankin score, and the synovialitis-score versus the DMM group. ConclusionOur results demonstrate that although Etoricoxib can relieve the pain induced by OA, it also has adverse effects on subchondral bone in early OA.

Misalignment Error in Cancellous Bone Apparent Elastic Modulus Depends on Bone Volume Fraction and Degree of Anisotropy

2020 ◽  
Vol 143 (2) ◽  
Author(s):  
Matthew B. L. Bennison ◽  
A. Keith Pilkey ◽  
W. Brent Lievers
Keyword(s):  
Mechanical Properties ◽  
Elastic Modulus ◽  
Cancellous Bone ◽  
Volume Fraction ◽  
Experimental Studies ◽  
Bone Volume ◽  
Bone Volume Fraction ◽  
Skeletal Site ◽  
Degree Of Anisotropy ◽  
Misalignment Error

Abstract Cancellous bone is an anisotropic structure with architectural and mechanical properties that vary due to both skeletal site and disease state. This anisotropy means that, in order to accurately and consistently measure the mechanical properties of cancellous bone, experiments should be performed along the primary mechanical axis (PMA), that is, the orientation in which the mechanical properties are at their maximum value. Unfortunately, some degree of misalignment will always be present, and the magnitude of the resulting error is expected to be architecture dependent. The goal of this work is to quantify the dependence of the misalignment error, expressed in terms of change in apparent elastic modulus (ΔE), on both the bone volume fraction (BV/TV) and the degree of anisotropy (DA). Finite element method (FEM) models of bovine cancellous bone from five different skeletal sites were created at 5 deg and 20 deg from the PMA determined for each region. An additional set of models was created using image dilation/erosion steps in order to control for BV/TV and better isolate the effect of DA. Misalignment error was found to increase with increasing DA and decreasing BV/TV. At 5 deg misaligned from the PMA, error is relatively low (<5%) in all cases but increases to 8–24% error at 20 deg. These results suggest that great care is needed to avoid introducing misalignment error into experimental studies, particularly when studying regions with high anisotropy and/or low bone volume fraction, such as vertebral or osteoporotic bone.

scholarly journals Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses

2011 ◽  
Vol 209 (1) ◽  
pp. 21-32 ◽  
Author(s):  
William F Powell ◽  
Kevin J Barry ◽  
Irena Tulum ◽  
Tatsuya Kobayashi ◽  
Stephen E Harris ◽  
...  
Keyword(s):  
Volume Fraction ◽  
Bone Structure ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Blood Calcium ◽  
Low Calcium Diet ◽  
Exon 1 ◽  
Skeletal Homeostasis ◽  
Pthrp Receptor

Parathyroid hormone (PTH) is a major physiologic regulator of calcium, phosphorous, and skeletal homeostasis. Cells of the osteoblastic lineage are key targets of PTH action in bone, and recent evidence suggests that osteocytes might be important in the anabolic effects of PTH. To understand the role of PTH signaling through the PTH/PTHrP receptors (PPR) in osteocytes and to determine the role(s) of these cells in mediating the effects of the hormone, we have generated mice in which PPR expression is specifically ablated in osteocytes. Transgenic mice in which the 10 kb-Dmp1 promoter drives a tamoxifen-inducible Cre-recombinase were mated with animals in which exon 1 of PPR is flanked by lox-P sites. In these animals, osteocyte-selective PPR knockout (Ocy-PPRcKO mice) could be induced by administration of tamoxifen. Histological analysis revealed a reduction in trabecular bone and mild osteopenia in Ocy-PPRcKO mice. Reduction of trabeculae number and thickness was also detected by micro-computed tomography analysis whereas bone volume fraction (BV/TV%) was unchanged. These findings were associated with an increase in Sost and sclerostin expression. When Ocy-PPRcKO mice were subjected to a low-calcium diet to induce secondary hyperparathyroidism, their blood calcium levels were significantly lower than littermate controls. Moreover, PTH was unable to suppress Sost and sclerostin expression in the Ocy-PPRcKO animals, suggesting an important role of PTH signaling in osteocytes for proper bone remodeling and calcium homeostasis.

scholarly journals Suppressed Osteocyte Perilacunar / Canalicular Remodeling Plays a Causal Role in Osteoarthritis

2019 ◽  
Author(s):  
Courtney M. Mazur ◽  
Jonathon J. Woo ◽  
Cristal S. Yee ◽  
Aaron J. Fields ◽  
Claire Acevedo ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Cartilage Degeneration ◽  
Causal Role ◽  
Knee Joints ◽  
Cellular Mechanisms ◽  
Primary Disorder ◽  
End Stage ◽  
Early Oa ◽  
Protease Expression

ABSTRACTOsteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. To determine if PLR suppression plays a causal role in OA, we ablated the PLR enzyme MMP13 in osteocytes, while leaving chondrocytic MMP13 intact. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, this osteocyte-intrinsic PLR defect was sufficient to reduce cartilage proteoglycan content and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, osteocyte PLR is a critical regulator of cartilage homeostasis. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and identify the causal role of suppressed perilacunar/canalicular remodeling in osteoarthritis.

scholarly journals Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis

2020 ◽  
Author(s):  
Shao-Hua Ping ◽  
Fa-Ming Tian ◽  
Hao Liu ◽  
Qi Sun ◽  
Li-Tao Shao ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Volume Fraction ◽  
Clinical Indication ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Ovx Rats ◽  
Tgf Β1

Overexpression of transforming growth factor-beta 1 (TGF-β1) and subchondral bone remodelling play key roles in osteoarthritis (OA). Raloxifene (RAL) reduces the serum level of TGF-β1 in postmenopausal women. However, the effect of RAL on TGF-β1 expression in articular cartilage is still unclear. Therefore, we aimed to investigate the protective effect of RAL on osteoporotic osteoarthritis via affecting TGF-β1 expression in cartilage and the metabolism of subchondral bone. Osteoporotic osteoarthritis was induced by a combination of anterior cruciate transection (ACLT) and ovariectomy (OVX). Rats were divided into five groups (n = 12): The sham group, the ACLT group, the OVX group, the ACLT + OVX group, and the RAL group (ACLT + OVX + RAL, 6.25 mg/kg/day for 12 weeks). Assessment was performed by histomorphology, microcomputed tomography (micro-CT) scan, immunohistochemistry, and tartrate-resistant acid phosphatase (TRAP) staining. We found that severe cartilage degeneration was shown in the ACLT + OVX group. The histomorphological scores, the levels of TGF-β1, and its related catabolic enzymes and osteoclasts numbers in the ACLT + OVX group were higher than those in other groups (p < 0.05). Furthermore, structure model index (SMI) and trabecular spacing (Tb.Sp) were decreased (p < 0.05), while bone mineral density (BMD), bone volume fraction (BV/TV), and trabecular number (Tb.N) were increased by RAL compared with the ACLT + OVX group (p < 0.05). Our findings demonstrated that RAL in clinical doses retards the development of osteoporotic osteoarthritis by inhibiting the overexpression of TGF-β1 in cartilage and regulating the metabolism of subchondral bone. These results provide support for RAL in the expansion of clinical indication for prevention and treatment in postmenopausal osteoarthritis.

MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

2020 ◽  
Vol 99 (13) ◽  
pp. 1469-1477
Author(s):  
J.L. Sun ◽  
J.F. Yan ◽  
S.B. Yu ◽  
J. Zhao ◽  
Q.Q. Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Loss ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Volume Fraction ◽  
Cartilage Degradation ◽  
Specific Inhibition ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

Abnormal subchondral bone remodeling plays important roles during osteoarthritis (OA) pathology. Recent studies show that bone marrow mesenchymal stem cells (BMSCs) in osteoarthritic subchondral bones exhibit a prominent pro-osteoclastic effect that contributes to abnormal subchondral bone remodeling; however, the pathologic mechanism remains unclear. In the present study, we used a mouse model with OA-like change in the temporomandibular joint (TMJ) induced by an experimentally unilateral anterior crossbite (UAC) and found that the level of microRNA-29b ( miR-29b), but not miR-29a or miR-29c, was markedly lower in BMSCs from subchondral bones of UAC mice as compared with that from the sham control mice. With an intra-articular aptamer delivery system, BMSC-specific overexpression of miR-29b by aptamer-agomiR-29b rescued subchondral bone loss and osteoclast hyperfunction in UAC mice, as demonstrated by a significant increase in bone mineral density, bone volume fraction, trabecular thickness, and the gene expression of osteocalcin and Runx2 but decreased trabecular separation, osteoclast number and osteoclast surface/bone surface, and the gene expression of cathepsin K, Trap, Wnt5a, Rankl, and Rank as compared with those in the UAC mice treated by aptamer-NC (all P < 0.05). In addition, BMSC-specific inhibition of miR-29b by aptamer-antagomiR-29b exacerbated those responses in UAC mice. Notably, although it primarily affected miR-29b levels in the subchondral bone (but not in cartilage and synovium), BMSC-specific overexpression of miR-29b in UAC mice largely rescued OA-like cartilage degradation, including decreased chondrocyte density, cartilage thickness, and the percentage areas of proteoglycans and type II collagen, while BMSC-specific inhibition of miR-29b aggravated these characteristics of cartilage degradation in UAC mice. Moreover, we identified Wnt5a, but not Rankl or Sdf-1, as the direct target of miR-29b. The results of the present study indicate that miR-29b is a key regulator of the pro-osteoclastic effects of BMSCs in TMJ-OA subchondral bones and plays important roles in the TMJ-OA progression.

scholarly journals Microstructure and mechanical properties of subchondral bone are negatively regulated by tramadol in osteoarthritis in mice

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Chen-Chen Ji ◽  
Bo Liu ◽  
Yi-Jie Shao ◽  
Ting Liang ◽  
Hua-Ye Jiang ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Subchondral Bone ◽  
Volume Fraction ◽  
Ct Scanning ◽  
Knee Joints ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Treatment Groups ◽  
Microstructure And Mechanical Properties ◽  
Histological Staining

Abstract Objectives: In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties. Methods: A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention. Results: In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not. Conclusion: Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints.

scholarly journals The role of calcified cartilage and subchondral bone in the initiation and progression of ochronotic arthropathy in alkaptonuria

2011 ◽  
Vol 63 (12) ◽  
pp. 3887-3896 ◽  
Author(s):  
A. M. Taylor ◽  
A. Boyde ◽  
P. J. M. Wilson ◽  
J. C. Jarvis ◽  
J. S. Davidson ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Ochronotic Arthropathy ◽  
Calcified Cartilage

scholarly journals Enzalutamide Reduces the Bone Mass in the Axial But Not the Appendicular Skeleton in Male Mice

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 969-977 ◽  
Author(s):  
Jianyao Wu ◽  
Sofia Movérare-Skrtic ◽  
Anna E. Börjesson ◽  
Marie K. Lagerquist ◽  
Klara Sjögren ◽  
...  
Keyword(s):  
Bone Mass ◽  
Sexual Maturation ◽  
Volume Fraction ◽  
Axial Skeleton ◽  
Bone Volume ◽  
Appendicular Skeleton ◽  
Trabecular Bone Volume ◽  
Male Mice ◽  
Bone Volume Fraction

Abstract Testosterone is a crucial regulator of the skeleton, but the role of the androgen receptor (AR) for the maintenance of the adult male skeleton is unclear. In the present study, the role of the AR for bone metabolism and skeletal growth after sexual maturation was evaluated by means of the drug enzalutamide, which is a new AR antagonist used in the treatment of prostate cancer patients. Nine-week-old male mice were treated with 10, 30, or 100 mg/kg·d of enzalutamide for 21 days or were surgically castrated and were compared with vehicle-treated gonadal intact mice. Although orchidectomy reduced the cortical bone thickness and trabecular bone volume fraction in the appendicular skeleton, these parameters were unaffected by enzalutamide. In contrast, both enzalutamide and orchidectomy reduced the bone mass in the axial skeleton as demonstrated by a reduced lumbar spine areal bone mineral density (P &lt; .001) and trabecular bone volume fraction in L5 vertebrae (P &lt; .001) compared with vehicle-treated gonadal intact mice. A compression test of the L5 vertebrae revealed that the mechanical strength in the axial skeleton was significantly reduced by enzalutamide (maximal load at failure −15.3% ± 3.5%; P &lt; .01). The effects of enzalutamide in the axial skeleton were associated with a high bone turnover. In conclusion, enzalutamide reduces the bone mass in the axial but not the appendicular skeleton in male mice after sexual maturation. We propose that the effect of testosterone on the axial skeleton in male mice is mainly mediated via the AR.

scholarly journals Pax5 Negatively Regulates Osteoclastogenesis through Downregulation of Blimp1

2021 ◽  
Vol 22 (4) ◽  
pp. 2097
Author(s):  
Jiyeon Yu ◽  
Sumi Kim ◽  
Nari Lee ◽  
Hyoeun Jeon ◽  
Jun Lee ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Volume Fraction ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Lineage Specification ◽  
Bone Volume Fraction ◽  
Trabecular Thickness ◽  
Negative Role

Paired box protein 5 (Pax5) is a crucial transcription factor responsible for B-cell lineage specification and commitment. In this study, we identified a negative role of Pax5 in osteoclastogenesis. The expression of Pax5 was time-dependently downregulated by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulation in osteoclastogenesis. Osteoclast (OC) differentiation and bone resorption were inhibited (68.9% and 48% reductions, respectively) by forced expression of Pax5 in OC lineage cells. Pax5 led to the induction of antiosteoclastogenic factors through downregulation of B lymphocyte-induced maturation protein 1 (Blimp1). To examine the negative role of Pax5 in vivo, we generated Pax5 transgenic (Pax5Tg) mice expressing the human Pax5 transgene under the control of the tartrate-resistant acid phosphatase (TRAP) promoter, which is expressed mainly in OC lineage cells. OC differentiation and bone resorption were inhibited (54.2–76.9% and 24.0–26.2% reductions, respectively) in Pax5Tg mice, thereby contributing to the osteopetrotic-like bone phenotype characterized by increased bone mineral density (13.0–13.6% higher), trabecular bone volume fraction (32.5–38.1% higher), trabecular thickness (8.4–9.0% higher), and trabecular number (25.5–26.7% higher) and decreased trabecular spacing (9.3–10.4% lower) compared to wild-type control mice. Furthermore, the number of OCs was decreased (48.8–65.3% reduction) in Pax5Tg mice. These findings indicate that Pax5 plays a negative role in OC lineage specification and commitment through Blimp1 downregulation. Thus, our data suggest that the Pax5–Blimp1 axis is crucial for the regulation of RANKL-induced osteoclastogenesis.

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