The postnatal skeleton undergoes growth, remodeling, and repair. We hypothesized that skeletal progenitor cells active during these disparate phases are genetically and phenotypically distinct. We identified a highly potent regenerative cell type that we term the fracture-induced bone, cartilage, stromal progenitor (f-BCSP) in the fracture callus of adult mice. The f-BCSP possesses significantly enhanced skeletogenic potential compared with BCSPs harvested from uninjured bone. It also recapitulates many gene expression patterns involved in perinatal skeletogenesis. Our results indicate that the skeletal progenitor population is functionally stratified, containing distinct subsets responsible for growth, regeneration, and repair. Furthermore, our findings suggest that injury-induced changes to the skeletal stem and progenitor microenvironments could activate these cells and enhance their regenerative potential.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538608 | PMC |
| http://dx.doi.org/10.1073/pnas.1513066112 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Local tissue response to a C-X-C motif chemokine ligand 12 therapy for fecal incontinence in a rabbit model.
Am J Physiol Gastrointest Liver Physiol
January 2025
Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.
This study aimed to determine if local injection of CXCL12 reduces sphincter fibrosis, restores sphincter muscle content, vascularization, and innervation, and recruits progenitor cells in a rabbit model of anal sphincter injury and incontinence. Adult female rabbits were assigned to 3 groups: uninjured/no treatment (control), injured/treated (treated), and injured/no treatment (untreated) (n=4 each). Injured groups were anesthetized and a section of external anal sphincter was removed at the 9:00 o'clock position.
View Article and Find Full Text PDFElevated EBF2 in mouse but not pig drives the progressive brown fat lineage specification via chromatin activation.
J Adv Res
December 2024
College of Animal Science, Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, Shandong Agricultural University, Taian, China; College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China. Electronic address:
Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, but it is absent in some mammals, including pigs. During development, BAT progenitors are derived from paired box 7 (Pax7)-expressing somitic mesodermal stem cells, which also give rise to skeletal muscle. However, the intrinsic mechanisms underlying the fate decisions between brown fat and muscle progenitors remain elusive.
View Article and Find Full Text PDFIntrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the mdx Mouse.
J Cachexia Sarcopenia Muscle
February 2025
Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Background: Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin-deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression.
Methods: Using the mdx mouse model of DMD, we performed an in-depth characterization of disease progression and MuSC function in dystrophin-deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays.
Modulation of the JAK2-STAT3 pathway promotes expansion and maturation of human iPSCs-derived myogenic progenitor cells.
bioRxiv
December 2024
Sanford Burnham Prebys Medical Discovery Institute, Development, Aging and Regeneration Program, La Jolla, CA 92037, USA.
Generation of induced pluripotent cells (hiPSCs)-derived skeletal muscle progenitor cells (SMPCs) holds great promise for regenerative medicine for skeletal muscle wasting diseases, as for example Duchenne Muscular Dystrophy (DMD). Multiple approaches, involving ectopic expression of key regulatory myogenic genes or small molecules cocktails, have been described by different groups to obtain SMPC towards cell-transplantation as a therapeutic approach to skeletal muscle diseases. However, hiPSCs-derived SMPC generated using transgene-free protocols are usually obtained in a low amount and resemble a more embryonal/fetal stage of differentiation.
View Article and Find Full Text PDFNEDD4 enhances bone‑tendon healing in rotator cuff tears by reducing fatty infiltration.
Mol Med Rep
March 2025
School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.
Rotator cuff tears (RCT) can cause shoulder pain, weakness and stiffness, significantly affecting daily life. Analysis of the GSE103266 dataset revealed significant changes in the mTOR/PI3K/Akt signaling pathway and lipid metabolism‑related pathways, suggesting that fatty infiltration may affect RCT. The analysis indicated that the ubiquitin ligase NEDD4 plays a critical role in RCT.
View Article and Find Full Text PDFWant 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!