AI Article Synopsis

Article Abstract

Osteoporosis is a progressive bone disease caused by an imbalance between bone resorption and formation. Recently, plasminogen activator inhibitor-1 (PAI-1) was shown to play an important role in bone metabolism using PAI-1-deficient mice. In this study, we evaluated the therapeutic benefits of novel, orally available small-molecule PAI-1 inhibitor (iPAI-1) in an estrogen deficiency-induced osteoporosis model. Eight-week-old C57BL/6J female mice were divided into three groups: a sham + vehicle (Sham), ovariectomy + vehicle (OVX + v), and OVX + iPAI-1 (OVX + i) group. iPAI-1 was administered orally each day for 6 weeks starting the day after the operation. Six weeks of iPAI-1 treatment prevented OVX-induced trabecular bone loss in both the femoral bone and lumbar spine. Bone formation activity was significantly higher in the OVX + i group than in the OVX + v and Sham groups. Unexpectedly, OVX-induced osteoclastogenesis was partially, but significantly reduced. Fluorescence-activated cell sorting analyses indicated that the number of bone marrow stromal cells was higher in the OVX + i group than that in the OVX + v group. A colony-forming unit-osteoblast assay indicated enhanced mineralized nodule formation activity in bone marrow cells isolated from iPAI-1-treated animals. Bone marrow ablation analysis indicated that the remodeled trabecular bone volume was significantly higher in the iPAI-1-treated group than that in the control group. In conclusion, our results suggest PAI-1 blockade via a small-molecule inhibitor is a new therapeutic approach for the anabolic treatment of postmenopausal osteoporosis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881535PMC
http://dx.doi.org/10.1002/2211-5463.12390DOI Listing

Publication Analysis

Top Keywords

bone
12
ovx + i group
12
bone marrow
12
small-molecule pai-1
8
pai-1 inhibitor
8
bone loss
8
bone formation
8
estrogen deficiency-induced
8
deficiency-induced osteoporosis
8
osteoporosis model
8

Similar Publications

Associations of fat, bone, and muscle indices with disease severity in patients with obstructive sleep apnea hypopnea syndrome.

Sleep Breath

January 2025

Department of Pulmonary and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1 Da Hua Road, Dong Dan, Dongcheng District, Beijing, 100730, PR China.

Purpose: To investigate the relationship between obstructive sleep apnea hypopnea syndrome (OSAHS) severity and fat, bone, and muscle indices.

Methods: This study included 102 patients with OSAHS and retrospectively reviewed their physical examination data. All patients underwent polysomnography, body composition analysis, dual-energy X-ray absorptiometry, computed tomography (CT) and blood test.

View Article and Find Full Text PDF

Objectives: To assess the effect of patient positioning and general anesthesia on the condylar position in orthognathic surgery.

Materials And Methods: This prospective study included patients undergoing orthognathic surgery between 2019 and 2020. Four weeks prior to surgery (T0) cone-beam computed tomography (CBCT) scans and intra-oral scans (IOS) were acquired in an upright position.

View Article and Find Full Text PDF

Reducing Healing Period with DDM/rhBMP-2 Grafting for Early Loading in Dental Implant Surgery.

Tissue Eng Regen Med

January 2025

Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, 172 Dolma-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.

Background: Traditionally, dental implants require a healing period of 4 to 9 months for osseointegration, with longer recovery times considered when bone grafting is needed. This retrospective study evaluates the clinical efficacy of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) during dental implant placement to expedite the osseointegration period for early loading.

Methods: Thirty patients (17 male, 13 female; mean age 55.

View Article and Find Full Text PDF

Background: Clavicle fractures associated with ipsilateral coracoid process fractures are very rare, with limited literature reporting only a few cases. This study reports on 27 patients with ipsilateral concomitant fractures of the clavicle and coracoid process who were followed for more than 12 months.

Material And Methods: This retrospective study reviewed the charts of skeletally mature patients with traumatic ipsilateral clavicle and coracoid process fractures treated at the authors' institution.

View Article and Find Full Text PDF

Background: Heterozygous TRPV4 mutations cause a group of skeletal dysplasias characterized by short stature, short trunk, and skeletal deformities.

Objective: The aim of this study is to compare the natural history of clinical and radiologic features of patients with different TRPV4-related skeletal dysplasias.

Materials And Methods: Thirteen patients with a mutation in TRPV4 were included in the study, and 11 were followed for a median of 6.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!