Study Design: Basic experiments in a mouse model of ossification of the posterior longitudinal ligament (OPLL).
Objective: To assess the osteogenic potential of mesenchymal stem cells (MSCs) obtained from muscle and adipose tissue in Tiptoe-walking (ttw) mice, in which cervical OPLL compresses the spinal cord and causes motor and sensory dysfunction.
Summary Of Background Data: In humans, MSCs have been implicated in the pathogenesis of cervical OPLL. Cervical OPLL in ttw mice causes chronic compression of the spinal cord. Few studies have compared the MSC osteogenic potential with behavioral changes in an OPLL animal model.
Methods: We compared the osteogenic potential and behavioral characteristics of MSCs from ttw mice (4 to 20 weeks old) with those from control wild-type mice (without hyperostosis). Ligament ossification was monitored by micro-computed tomography and pathology; tissues were double stained with fluorescent antibodies against markers for MSCs (CD45 and CD105), at 8 weeks. The Basso Mouse Scale was used to assess motor function, and heat and mechanical tests to assess sensory function. The osteogenic potential of adipose and muscle MSCs was assessed by Alizarin Red S absorbance, staining for osteogenic mineralization, and real-time quantitative polymerase chain reaction for osteogenesis-related genes.
Results: Spinal-ligament ossification began in ttw mice at 8 weeks of age, and the ossified area increased with age. Immunofluorescence staining identified MSCs in the ossification area. The ttw mice became hyposensitive at 8 weeks of age, and Basso Mouse Scale scores showed motor-function deficits starting at 12 weeks of age. Alizarin Red S staining for mineralization showed a higher osteogenic potential in the adipose- and muscle-derived MSCs from ttw mice than from wild-type mice at 4, 8, and 20 weeks of age. Real-time quantitative polymerase chain reaction showed that ttw MSCs strongly expressed osteogenesis-related genes.
Conclusion: MSCs derived from muscle and adipose tissue in ttw mice had a high osteogenic potential.
Level Of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000002266 | DOI Listing |
Sci Rep
January 2025
Department of Orthopaedics, Jichi Medical University School of Medicine, Tochigi, 329-0498, Japan.
Ossification of the posterior longitudinal ligament of the vertebral column (OPLL) is a disease characterised by ectopic bone formation in the spinal ligament that causes progressive neurological impairment. However, there are no suitable treatments for OPLL. Here, we compared the general characteristics and haemostasis of patients with OPLL and those with cervical spondylotic myelopathy.
View Article and Find Full Text PDFImmunity
January 2025
Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:
While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model.
View Article and Find Full Text PDFAntioxidants (Basel)
July 2024
Department of Orthodontics, School of Dental Medicine, Tsurumi University, Yokohama 230-8501, Kanagawa, Japan.
Calcification plays a key role in biological processes, and breakdown of the regulatory mechanism results in a pathological state such as ectopic calcification. We hypothesized that ENPP1, the enzyme that produces the calcification inhibitor pyrophosphate, is transcriptionally regulated by Nrf2, and that Nrf2 activation augments ENPP1 expression to inhibit ectopic calcification. Cell culture experiments were performed using mouse osteoblastic cell line MC3T3-E1.
View Article and Find Full Text PDFCells
June 2024
Research and Development, Inozyme Pharma, 321 Summer St, Suite 400, Boston, MA 02201, USA.
The Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) ectoenzyme regulates vascular intimal proliferation and mineralization of bone and soft tissues. variants cause Generalized Arterial Calcification of Infancy (GACI), a rare genetic disorder characterized by ectopic calcification, intimal proliferation, and stenosis of large- and medium-sized arteries. ENPP1 hydrolyzes extracellular ATP to pyrophosphate (PP) and AMP.
View Article and Find Full Text PDFJ Physiol
December 2023
Netherlands Institute for Neuroscience Amsterdam, Amsterdam, the Netherlands.
In Nyx mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, i.e. nystagmus.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!