miRNA-seq analysis of high glucose induced osteoblasts provides insight into the mechanism underlying diabetic osteoporosis.

The present study aims to explore the etiology of Diabetic osteoporosis (DOP), a chronic complication associated with diabetes mellitus. Specifically, the research seeks to identify potential miRNA biomarkers of DOP and investigated role in regulating osteoblasts. To achieve this, an animal model of DOP was established through the administration of a high-sugar and high-fat diet, and then injection of streptozotocin. Bone microarchitecture and histopathology analysis were analyzed. Rat calvarial osteoblasts (ROBs) were stimulated with high glucose (HG). MiRNA profiles of the stimulated osteoblasts were compared to control osteoblasts using sequencing. Proliferation and mineralization abilities were assessed using MTT assay, alkaline phosphatase, and alizarin red staining. Expression levels of OGN, Runx2, and ALP were determined through qRT-PCR and Western blot. MiRNA-sequencing results revealed increased miRNA-702-5p levels. Luciferase reporter gene was utilized to study the correlation between miR-702-5p and OGN. High glucose impaired cell proliferation and mineralization in vitro by inhibiting OGN, Runx2, and ALP expressions. Interference with miR-702-5p decreased OGN, Runx2, and ALP levels, which were restored by OGN overexpression. Additionally, downregulation of OGN and Runx2 in DOP rat femurs was confirmed. Therefore, the miRNA-702-5p/OGN/Runx2 signaling axis may play a role in DOP, and could be diagnostic biomarker and therapeutic target for not only DOP but also other forms of osteoporosis.

Sclerotic zone in femoral head necrosis: from pathophysiology to therapeutic implications.

This review summarizes the sclerotic zone's pathophysiology, characterization, formation process, and impact on femoral head necrosis. The sclerotic zone is a reaction interface formed during the repair of femoral head necrosis. Compared with normal bone tissue, the mechanical properties of the sclerotic zone are significantly enhanced. Many factors influence the formation of the sclerotic zone, including mechanics, bone metabolism, angiogenesis, and other biological processes. The sclerotic zone plays an essential role in preventing the collapse of the femoral head and can predict the risk of the collapse of the femoral head. Regulating the formation of the sclerotic zone of the femoral head has become a direction worthy of study in treating femoral head necrosis.

Bone grafting for femoral head necrosis in the past decade: a systematic review and network meta-analysis.

BACKGROUND: Bone grafting is considered a method that can provide mechanical and structural support to the femoral head and prevent the collapse of the femoral head after core decompression (CD). However, there are no consensus guidelines on which bone grafting method is best after CD. The authors assessed the efficacy of various bone grafting modalities and CD through a Bayesian network meta-analysis (NMA). MATERIALS AND METHODS: Ten articles were retrieved from PubMed, ScienceDirect, and Cochrane Library searches. Bone graft modalities are categorized into four, and CD is the control group: (1) CD, (2) autologous bone graft (ABG), (3) biomaterial bone graft (BBG), (4) bone graft combined with bone marrow graft (BG+BM), and (5) free vascular bone graft (FVBG). The rates of conversion to total hip arthroplasty (THA), femoral head necrosis progression rate, and Harris hip score (HHS) improvement were compared among the five treatments. RESULTS: A total of 816 hips were included in the NMA: specifically, 118 hips in CD, 334 in ABG, 133 in BBG, 113 in BG+BM, and 118 in FVBG. The NMA results show no significant differences in preventing conversion to THA and improving HHS in each group. All bone graft methods are better than CD in preventing osteonecrosis of the femoral head (ONFH) progress [ABG: odds ratio (OR)=0.21, 95% CI: 0.07-0.56; BBG: OR=0.13, 95% CI: 0.03-0.52; BG+BM: OR=0.06, 95% CI: 0.01-0.24; FVBG: OR=0.11, 95% CI: 0.02-0.38]. The rankgrams indicate that BG+BM is the best intervention in preventing conversion to THA (73%), preventing ONFH progress (75%), and improving HHS (57%), followed by the BBG in preventing conversion to THA (54%), improving HHS (38%), and the FVBG in preventing ONFH progress (42%). CONCLUSIONS: This finding indicates that bone grafting after CD is necessary to prevent ONFH progression. Moreover, bone grafts combined with bone marrow grafts and BBG seem to be effective treatment methods in ONFH.

The effects of nano-hydroxyapatite/polyamide 66 scaffold on dog femoral head osteonecrosis model: a preclinical study.

The lack of mechanical support in the bone tunnel formed after CD often results in a poor therapeutic effect in ONFH. The n-HA/P66 has excellent biocompatibility and mechanical properties and has been widely used in bone regeneration. The present study aimed to evaluate the effects of n-HA/P66 scaffold treatment in a dog model of ONFH. A FEA was performed to analyze the mechanical changes in the femoral head after CD and n-HA/P66 scaffold or tantalum rod implantation. Fifteen male beagles were selected to establish the model of ONFH by liquid nitrogen freezing method, and the models were identified by x-ray and MRI 4 weeks after modeling and randomly divided into three groups. Nine weeks later, femoral head samples were taken for morphology, micro-CT, and histological examination. The FEA showed that the n-HA/P66 scaffold proved the structural support in the bone tunnel, similar to the tantalum rod. The morphology showed that the femoral head with n-HA/P66 implantation is intact, while the femoral heads in the model group and CD group are collapsing. Moreover, the micro-CT results of the n-HA/P66 scaffold group were better than the model group and the CD group, and the interface between the n-HA/P66 scaffold and bone tissue is blurred. Furthermore, the histological result also verifies the alterations in micro-CT, and bone tissue grows in the bone tunnel with n-HA/P66 scaffold implanted while few in the CD group. The CD results in a lack of mechanical support in the femoral head subchondral bone and bone tunnel high stress. The n-HA/P66 scaffold implantation can provide mechanical support and relieve high stress induced by CD. The n-HA/P66 scaffold can treat femoral head necrosis and provide the bone tissue growth scaffold for the femoral head after CD to promote bone tissue regeneration.