Osteoking Promotes Bone Formation and Bone Defect Repair through ZBP1-STAT1-PKR-MLKL-mediated Necroptosis DOI Creative Commons
Suya Zhang, Yudong Liu,

Zhaochen Ma

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 30, 2023

Abstract Background: Osteoking has been used for fracture therapy with a satisfying clinical efficacy. However, its therapeutic properties and the underlying mechanisms remain elusive. Method: A bone defect rat model was established to evaluate pharmacological effects of by dynamic observation X-ray, micro-CT histopathologic examination. Transcriptome profiling performed identify defect-related genes effective targets. Then, "disease-related gene-drug target" interaction network constructed list key targets were screened, which experimentally verified. Results: effectively promoted repair in rats accelerating cortical growth trabeculae. Histopathologically, displayed lower scores bone, cancellous connection than normal controls, exerted favorable effect dose-dependent manner (all P<0.001). The abnormal serum levels turnover markers, factors metabolism-related biochemical indexes also reversed treatment. Following transcriptome-based investigation, we hypothesized that osteoking might attenuate ZBP1-STAT1-PKR-MLKL-mediated necroptosis involved into defect. Experimentally, expression ZBP1, STAT1, PKR hallmark inflammatory cytokines end distinctly elevated rats, but all treatment, suppressed activities RIPK1, RIPK3 MLKL tissue supernatants. Conclusions: may promote formation regulating ZBP1-STAT1-PKR axis, leading inhibit RIPK1/RIPK3/MLKL activation-mediated necroptosis.

Язык: Английский

Systematical Mutational Analysis of FRATtide against Osteoclast Differentiation by Alanine Scanning DOI
Yi Yang,

Chenchen Geng,

Huaxing Shen

и другие.

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 15(8), С. 1242 - 1249

Опубликована: Июль 10, 2024

Osteoporosis, a global bone disease, results in decreased density, mass, and microarchitecture deterioration, increasing fracture risk. In previous research, FRATtide, peptide derived from glycogen synthase kinase-3 binding protein, effectively hindered osteoclast differentiation to yield therapeutically potent derivatives via single double stapling. However, FRATtide's structure-activity relationship remains unclear. This study synthesized 25 FRATtide-derived peptides through systematic alanine scanning evaluated their activities. Substitutions Pro2, Leu5, Leu9, Val10, Leu11, Ser12, Asn14, Leu15, Ile16, Glu18, Arg22, Ser25, Arg26 showed reduced activity, while FRT13 FRT20 with Gly13 Arg21 substitutions, respectively, displayed enhanced F-actin resorption assays on better inhibition of compared FRATtide. elucidated relationship, thereby facilitating future structural optimization for osteoporosis treatment.

Язык: Английский

Процитировано

0
Macrophages and the musculoskeletal system DOI
Jiří Gallo, Stuart B. Goodman

Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 99 - 168

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

0
Endochondral Ossification for Spinal Fusion: A Novel Perspective from Biological Mechanisms to Clinical Applications DOI Open Access

Rile Ge,

Chenjun Liu, Yuhong Zhao

и другие.

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(9), С. 957 - 957

Опубликована: Сен. 9, 2024

Degenerative scoliosis (DS), encompassing conditions like spondylolisthesis and spinal stenosis, is a common type of deformity. Lumbar interbody fusion (LIF) stands as conventional surgical intervention for this ailment, aiming at decompression, restoration intervertebral height, stabilization motion segments. Despite its widespread use, the precise mechanism underlying remains elusive. In review, our focus lies on endochondral ossification fusion, process involving vertebral development bone healing. Endochondral key step successful fusion. can persist in hypoxic promote parallel angiogenesis osteogenesis, which corresponds to new formation region between vertebrae. The ideal material cages should have following characteristics: (1) Good biocompatibility; (2) Stable chemical properties; (3) Biomechanical properties similar tissue; (4) Promotion fusion; (5) Favorable imaging observation; (6) Biodegradability. Utilizing cartilage-derived bone-like constructs holds promise promoting bony post-operation, thus warranting exploration context procedures.

Язык: Английский

Процитировано

0
Osteoking Promotes Bone Formation and Bone Defect Repair through ZBP1-STAT1-PKR-MLKL-mediated Necroptosis DOI Creative Commons
Suya Zhang, Yudong Liu,

Zhaochen Ma

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 30, 2023

Abstract Background: Osteoking has been used for fracture therapy with a satisfying clinical efficacy. However, its therapeutic properties and the underlying mechanisms remain elusive. Method: A bone defect rat model was established to evaluate pharmacological effects of by dynamic observation X-ray, micro-CT histopathologic examination. Transcriptome profiling performed identify defect-related genes effective targets. Then, "disease-related gene-drug target" interaction network constructed list key targets were screened, which experimentally verified. Results: effectively promoted repair in rats accelerating cortical growth trabeculae. Histopathologically, displayed lower scores bone, cancellous connection than normal controls, exerted favorable effect dose-dependent manner (all P<0.001). The abnormal serum levels turnover markers, factors metabolism-related biochemical indexes also reversed treatment. Following transcriptome-based investigation, we hypothesized that osteoking might attenuate ZBP1-STAT1-PKR-MLKL-mediated necroptosis involved into defect. Experimentally, expression ZBP1, STAT1, PKR hallmark inflammatory cytokines end distinctly elevated rats, but all treatment, suppressed activities RIPK1, RIPK3 MLKL tissue supernatants. Conclusions: may promote formation regulating ZBP1-STAT1-PKR axis, leading inhibit RIPK1/RIPK3/MLKL activation-mediated necroptosis.

Язык: Английский

Процитировано

0