The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity.

Osteoporosis is a common chronic metabolic bone disorder. Recently, increasing numbers of studies have demonstrated that Toll-like receptor 4 (TLR4, a receptor located on the surface of osteoclasts and osteoblasts) plays a pivotal role in the development of osteoporosis. Herein, we performed a comprehensive review to summarize the findings from the relevant studies within this topic. Clinical data showed that TLR4 polymorphisms and aberrant TLR4 expression have been associated with the clinical significance of osteoporosis. Mechanistically, dysregulation of osteoblasts and osteoclasts induced by abnormal expression of TLR4 is the main molecular mechanism underlying the pathological processes of osteoporosis, which may be associated with the interactions between TLR4 and NF-κB pathway, proinflammatory effects, ncRNAs, and RUNX2. In vivo and in vitro studies demonstrate that many promising substances or agents (i.e., methionine, dioscin, miR-1906 mimic, artesunate, AEG-1 deletion, patchouli alcohol, and Bacteroides vulgatus) have been able to improve bone metabolism (i.e., inhibits bone resorption and promotes bone formation), which may partially attribute to the inhibition of TLR4 expression. The present review highlights the important role of TLR4 in the clinical significance and the pathogenesis of osteoporosis from the aspects of inflammation and immunity. Future therapeutic strategies targeting TLR4 may provide a new insight for osteoporosis treatment.

A Radiographic Analysis of Coronal Morphological Parameters of Lower Limbs in Chinese Non-knee Osteoarthritis Populations.

OBJECTIVES: Analyzing the lower limb coronal morphological parameters in populations without knee osteoarthritis (KOA) holds significant value in predicting, diagnosing, and formulating surgical strategies for KOA. This study aimed to comprehensively analyze the variability in these parameters among Chinese non-KOA populations, employing a substantial sample size. METHODS: A cross-sectional retrospective analysis was performed on the Chinese non-KOA populations (n = 407; 49.9% females). The study employed an in-house developed artificial intelligence software to meticulously assess the coronal morphological parameters of all 814 lower limbs. The parameters evaluated included the hip-knee-ankle angle (HKAA), weight-bearing line ratio (WBLR), joint line convergence angle (JLCA), mechanical lateral-proximal-femoral angle (mLPFA), mechanical lateral-distal-femoral angle (mLDFA), mechanical medial-proximal-tibial angle (mMPTA), and mechanical lateral-distal-tibial angle (mLDTA). Differences in these parameters were compared between left and right limbs, different genders, and different age groups (with 50 years as the cut-off point). RESULTS: HKAA and JLCA exhibited left-right differences (left vs. right: 178.2° ± 3.0° vs. 178.6° ± 2.9° for HKAA, p = 0.001; and 1.8° ± 1.5° vs. 1.4° ± 1.6° for JLCA, p < 0.001); except for the mLPFA, all other parameters show gender-related differences (male vs. female: 177.9° ± 2.8° vs. 179.0° ± 3.0° for HKAA, p < 0.001; 1.5° ± 1.5° vs. 1.8° ± 1.7° for JLCA, p = 0.003; 87.1° ± 2.1° vs. 88.1° ± 2.1° for mMPTA, p < 0.001; 90.2° ± 4.0° vs. 91.1° ± 3.2° for mLDTA, p < 0.001; 38.7% ± 12.9% vs. 43.6% ± 14.1% for WBLR, p < 0.001; and 87.7° ± 2.3° vs. 87.4° ± 2.7° for mLDTA, p = 0.045); mLPFA increase with age (younger vs. older: 90.1° ± 7.2° vs. 93.4° ± 4.9° for mLPFA, p < 0.001), while no statistical difference exists for other parameters. CONCLUSIONS: There were differences in lower limb coronal morphological parameters among Chinese non-KOA populations between left and right sides, different genders, and age.

The best position of bone grafts in the medial open-wedge high tibial osteotomy: A finite element analysis.

BACKGROUND AND OBJECTIVE: The application of wedge-shaped bone grafts can increase the biomechanical stability of knee during the medial open-wedge high tibial osteotomy (MOWHTO) by reducing the von Mises stress of the medial plate and lateral cortical hinge area. However, the optimal position of bone grafts it remains unclear, so we aimed to determine search for the optimal position of the bone grafts in MOWHTO by using finite element analysis. METHODS: In the finite element analysis, MOWHTO models were established with three different osteotomy distraction heights and assembled into four groups according to different conditions, including the no bone grafts (NBG) group, the anterior bone grafts (ABG) group, the middle bone grafts (MBG) group, and the posterior bone grafts (PBG) group. Based on previous studies, 600 N and 1800 N loads were applied to the knee joint to simulate the static forces during a double and single leg stance to measure the von Mises stress of the medial implant area and lateral hinge area, the maximum displacement of different models, the relative displacement of the osteotomy area and the stress distribution in the bone grafts. RESULTS: Compared to the NBG and ABG groups, the stress of the lateral cortical hinge area and the medial implate area was significantly lower in the PBG group. For example, under the 600N force load, when the height of the osteotomy area was 10 mm, 15 mm, and 20 mm, the maximum von Mises stress of the medial implate area and lateral cortical hinge area in the NBG group were 140, 141, 172, and 53, 57, 60 MPa, respectively. Compared with the NBG group, the maximum von Mises stress of the medial implate area and lateral cortical hinge area in the PBG group were reduced by 45%, 56%, 63% and 14%, 39%, 68% at distraction height of 10 mm, 15 mm, and 20 mm, respectively. The bone grafts in the posterior parts provide the best stability,with the stress of the middle and posterior bone grafts are mainly concentrated in the edge. CONCLUSIONS: The posterior part of the osteotomy area is the best position for bone graft placement since it provides optimal stability and reduces von Mises stress in the medial plate and lateral cortex hinge area, with the stress of the posterior bone grafts mainly concentrated in the edge. These findings guide bone graft placement sites in clinical surgery and are a basis for future research on bone graft materials and structures in MOWHTO.

N-Methyl Pyrrolidone (NMP) Alleviates Lipopolysaccharide (LPS)-Induced Inflammatory Injury in Articular Chondrocytes.

BACKGROUND Studies on the chondrocyte inflammatory injury are very important for understanding the pathogenesis and clinical treatment of osteoarthritis (OA). Evidence suggests that N-methyl pyrrolidone (NMP) may be used as an adjuvant therapy alongside established methods of OA treatment. This study investigated the effect of NMP on chondrocyte inflammatory injury and explored the underlying molecular mechanism. MATERIAL AND METHODS To mimic the inflammatory injury in vitro, the articular chondrocyte line ATDC5 was simulated with lipopolysaccharide (LPS). ATDC5 cells were treated with various concentrations of NMP (0, 5, and 10 nM). Cell viability was measured using CCK-8 assay; cell apoptosis was detected using FCM; related protein and mRNA expressions were determined using Western blot assay and qRT-PCR assay; and inflammatory factors (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-8) productions were measured by performing ELISA assay. RESULTS The results showed that LPS simulation repressed ATDC5 cell viability, prompted cell apoptosis, and enhanced the secretion of inflammatory factors. NMP treatment reduced inflammatory injury induced by LPS in a dose-dependent manner. Furthermore, NMP inhibited the activation of JNK and p38 pathways. In addition, inhibition of NF-κB activation was observed following NMP treatment. CONCLUSIONS NMP prevents inflammatory reaction of articular chondrocytes via repressing the MAPK/NF-kB pathway. Our findings provide a promising therapeutic agent for OA treatment.