RESUMO
Background: Abnormal osteoclast and osteoblast differentiation is an essential pathological process in osteoporosis. As an important deubiquitinase enzyme, ubiquitin-specific peptidase 7 (USP7) participates in various disease processes through posttranslational modification. However, the mechanism by which USP7 regulates osteoporosis remains unknown. Herein, we aimed to investigate whether USP7 regulates abnormal osteoclast differentiation in osteoporosis. Methods: The gene expression profiles of blood monocytes were preprocessed to analyze the differential expression of USP genes. CD14+ peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from osteoporosis patients (OPs) and healthy donors (HDs), and the expression pattern of USP7 during the differentiation of CD14+ PBMCs into osteoclasts was detected by western blotting. The role of USP7 in the osteoclast differentiation of PBMCs treated with USP7 siRNA or exogenous rUSP7 was further investigated by the F-actin assay, TRAP staining and western blotting. Moreover, the interaction between high-mobility group protein 1 (HMGB1) and USP7 was investigated by coimmunoprecipitation, and the regulation of the USP7-HMGB1 axis in osteoclast differentiation was further verified. Osteoporosis in ovariectomized (OVX) mice was then studied using the USP7-specific inhibitor P5091 to identify the role of USP7 in osteoporosis. Results: The bioinformatic analyses and CD14+ PBMCs from osteoporosis patients confirmed that the upregulation of USP7 was associated with osteoporosis. USP7 positively regulates the osteoclast differentiation of CD14+ PBMCs in vitro. Mechanistically, USP7 promoted osteoclast formation by binding to and deubiquitination of HMGB1. In vivo, P5091 effectively attenuates bone loss in OVX mice. Conclusion: We demonstrate that USP7 promotes the differentiation of CD14+ PBMCs into osteoclasts via HMGB1 deubiquitination and that inhibition of USP7 effectively attenuates bone loss in osteoporosis in vivo.The translational potential of this article:The study reveals novel insights into the role of USP7 in the progression of osteoporosis and provides a new therapeutic target for the treatment of osteoporosis.
RESUMO
Background: Currently, change in pelvic incidence (PI) in patients after spinal surgery have not been associated with clear clinical symptoms. This study sought to compare changes in the sagittal parameters of different patients before and after thoracolumbar spine surgery, the relationship between PI change and sacroiliac joint pain (SIJP) after surgery was clarified, and the correlation between PI change and sacroiliac joint (SIJ) activity was verified. Methods: This study retrospectively analyzed the data of patients who underwent thoracolumbar fusion at Sun Yat-sen Memorial Hospital from January 2019 to June 2021. The spinal and pelvic parameters [including pelvic tilt (PT), sacral slope (SS), PI, lumbar lordosis (LL) angle, etc.] of 409 patients with standard standing lateral radiographs before and after surgery were compared and analyzed. Postoperative follow-up of all patients with standardized SIJP assessment. The incidence of postoperative SIJP, and its correlation with sagittal parameters of the spine and pelvis, surgical methods, and the basic characteristics of patients were analyzed. The Chi-square test was used for categorical variables, the independent-sample t-test was used for generally conformed normally distributed continuous variables. Risk factors associated with the development of SIJP were analyzed using logistics regression. Correlations among SS, PI, and the 4 other sagittal parameters were analyzed using the Pearson correlation coefficient (r). Results: Postoperative PI changes tended to be larger in the lowest instrumented vertebra (LIV) (L4 and above: 1.63°; L5: 2.43°; S1: 3.83°; P<0.05) and longer fixed segment. The risk factors for SIJP included a PI >4° [odds ratio (OR) =13.051; P<0.001], LIV S1 (OR =3.378; P=0.023), and fixed total segment ≥3 (OR =2.632; P=0.038). ∆PI was significantly correlated with ∆SS in patients with non-S1 distal fixation vertebrae (R2=0.388; P<0.01), but no such correlation was found in patients with S1 distal fixation vertebrate. Conclusions: Changes in PI values after thoracolumbar spine surgery can correctly reflect the motion state of the SIJ. Excessive changes in PI (>4°) are similar to the mechanism of distal junctional kyphosis (DJK), while such changes make patients prone to SIJP following lumbar spine surgery.