Stimulation of fracture mineralization by salt-inducible kinase inhibitors.

ABSTRACT:

Introduction

Over 6.8 million fractures occur annually in the US, with 10% experiencing delayed- or non-union. Anabolic therapeutics like PTH analogs stimulate fracture repair, and small molecule salt inducible kinase (SIK) inhibitors mimic PTH action. This study tests whether the SIK inhibitor YKL-05-099 accelerates fracture callus osteogenesis.

Methods

126 female mice underwent femoral shaft pinning and midshaft fracture, receiving daily injections of PBS, YKL-05-099, or PTH. Callus tissues were analyzed via RT-qPCR, histology, single-cell RNA-seq, and μCT imaging. Biomechanical testing evaluated tissue rigidity. A hydrogel-based delivery system for PTH and siRNAs targeting SIK2/SIK3 was developed and tested.

Results

YKL-05-099 and PTH-treated mice showed higher min

SUBMITTER: Momenzadeh K 

PROVIDER: S-EPMC11445660 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature