Aims Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Methods Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. Results Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group. Conclusion Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway. Cite this article: Bone Joint Res 2020;9(10):675–688.
Background Although adjacent segmental intervertebral disc degeneration (ASDD) is one of the most common complications after lumbar fusion, its exact mechanism remains unclear. As an antibody to RANKL, denosumab (Dmab) effectively reduces bone resorption and stimulates bone formation, which can increase bone mineral density (BMD) and improve osteoporosis. However, it has not been confirmed whether Dmab has a reversing or retarding effect on ASDD. Methods Three-month-old female Sprague-Dawley rats that underwent L4–L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after bilateral ovariectomy (OVX) surgery were given Dmab 4 weeks after PLF surgery (OVX+PLF+Dmab group). In addition, the following control groups were defined: Sham, OVX, PLF, and OVX+PLF (n=12 each). Next, manual palpation and X-ray were used to evaluate the state of lumbar fusion. The bone microstructure in the lumbar vertebra and endplate as well as the disc height index (DHI) of L5/6 was evaluated by microcomputed tomography (μCT). The characteristic alterations of ASDD were identified via Safranin-O green staining. Osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining, and the biomechanical properties of vertebrae were evaluated. Aggrecan (Agg), metalloproteinase-13 (MMP-13), and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) expression in the intervertebral disc were detected by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) analysis. In addition, the expression of CD24 and Sox-9 was assessed by immunohistochemistry. Results Manual palpation showed clear evidence of the fused segment’s immobility. Compared to the OVX+PLF group, more new bone formation was observed by X-ray examination in the OVX+PLF+Dmab group. Dmab significantly alleviated ASDD by retaining disc height index (DHI), decreasing endplate porosity, and increasing vertebral biomechanical properties and BMD. TRAP staining results showed a significantly decreased number of active osteoclasts after Dmab treatment, especially in subchondral bone and cartilaginous endplates. Moreover, the protein and mRNA expression results in discs (IVDs) showed that Dmab not only inhibited matrix degradation by decreasing MMP-13 and ADAMTS-4 but also promoted matrix synthesis by increasing Agg. Dmab maintained the number of notochord cells by increasing CD24 but reducing Sox-9. Conclusions These results suggest that Dmab may be a novel therapeutic target for ASDD treatment.
Objective: To assess the effects of PTH (1-34) on bone and cartilage metabolism in a collagenase-induced mouse model of osteoarthritis (OA) and examine whether PTH (1-34) affects the expression of JAK2/STAT3 and WNT5A/ROR2 in this process.Methods: Eighteen 12-week-old male C57Bl/6 mice were randomly assigned into three groups as follows: sham group (Group A), the collagenase + saline injection group (Group B), and the collagenase + PTH (1-34) treatment group (Group C). Collagenase was injected (intra-articular) into the knee joint of Group B and C. The PTH (1-34)-treatment was started at 6 weeks after the operation and lasted for 6 weeks. Cartilage pathology was evaluated by gross visual, histological, and immunohistochemical assessments. Subchondral bone was evaluated by microcomputed tomography (micro-CT) and immunohistochemical analyses. Results:The OARSI macroscopic and microscopic scores of Group B were higher than those of Group A (P = 0.026; P = 0.002, respectively). Group C showed statistically significant differences in macroscopic and microscopic scores from Group B (P = 0.041; P = 0.008, respectively). The results showed that the Col-II and AGG expression levels in the cartilage tissue were significantly lower in Group B than Group A
In recent years, along with the development and application of magnesium alloys, magnesium alloys have been widely used in automotive, aerospace, medicine, sports, and other fields. In the field of medical materials, magnesium not only has the advantage of light weight, high strength, and a density similar to that of human bone, but also has good biocompatibility and promotes the growth of human bone. However, the mechanical properties and corrosion resistance of magnesium alloys need to be further improved to meet the requirements for human biodegradable implants. In this study, three alloys (mass fractions: Mg–10Zn, Mg–20Zn, and Mg–30Zn (wt.%)) were prepared using powder metallurgy by homogeneously mixing powders of the above materials in a certain amount with magnesium as the substrate through the addition of zinc elements, which also have good biocompatibility. The effect of zinc on the microstructure, mechanical properties, wear performance, and corrosion resistance of magnesium–zinc alloys was studied when the zinc content was different. The results show that compared with the traditional magnesium alloy using powder metallurgy, prepared magnesium alloy has good resistance to compression and bending, its maximum compressive stress can reach up to 318.96 MPa, the maximum bending strength reached 189.41 MPa, and can meet the mechanical properties of the alloy as a human bone-plate requirements. On the polarization curve, the maximum positive shift of corrosion potential of the specimens was 73 mv and the maximum decrease of corrosion-current density was 53.2%. From the comparison of the above properties, it was concluded that the three prepared alloys of which Mg–20% Zn had the best overall performance. Its maximum compressive stress, maximum bending strength, and corrosion-current density reached 318.96 MPa, 189.41 MPa and 2.08 × 10−5 A·cm−2 respectively, which are more suitable for use as human implant bone splints in human-body fluid environment.
Magnesium alloy, as an absorbable and implantable biomaterial, has been greatly developed in the application field of biomaterials in recent years due to its excellent biocompatibility and biomechanics. However, due to the poor corrosion resistance of magnesium alloy in the physiological environment, the degradation rate will be unbalanced, which seriously affects the clinical use. There are two main ways to improve the corrosion resistance of magnesium alloy: one is by adding alloying elements, the other is by surface modification technology. Compared with adding alloy elements, the surface coating modification has the following advantages: (1) The surface coating modification is carried out without changing the matrix elements of magnesium alloy, avoiding the introduction of other elements; (2) The corrosion resistance of magnesium alloy can be improved by relatively simple physical, chemical, or electrochemical improvement. From the perspective of corrosion resistance and biocompatibility of biomedical magnesium alloy materials, this paper summarizes the application and characteristics of six different surface coating modifications in the biomedical magnesium alloy field, including chemical conversion method, micro-arc oxidation method, sol-gel method, electrophoretic deposition, hydrothermal method, and thermal spraying method. In the last section, it looks forward to the development prospect of surface coating modification and points out that preparing modified coatings on the implant surface combined with various modification post-treatment technologies is the main direction to improve biocompatibility and realize clinical functionalization.
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