The effects of primary cilia-mediated mechanical stimulation on nestin+-BMSCs during bone-tendon healing.
J Adv Res
; 2024 Sep 19.
Article
en En
| MEDLINE
| ID: mdl-39306273
ABSTRACT
INTRODUCTION:
Mechanical stimulation has been proven to promote bone-tendon interface (BTI) healing, but the mechanism remains unclear.OBJECTIVE:
To investigate the effects of mechanical stimulation on the biological behavior of nestin+-bone mesenchymal stem cells (BMSCs) during the BTI healing, and to reveal the mechanisms of mechanical stimulation affecting BTI healing by primary cilia on the nestin+-BMSCs.METHODS:
Transgenic tracing mice (nestin creERT2 IFT88fl/fl/ROSA26 YFP) with primary cilia on nestin+-BMSCs conditioned knocked out were constructed, and the littermates (nestin creERT2 ROSA26 YFP) with normal cilia on nestin+-BMSCs were the control. After establishing mouse supraspinatus insertion injury models, samples were collected at week-2 (n = 5 per group), 4 and 8 (n = 15 per group, respectively). In vivo, the repair efficiency was evaluated by histology, imaging, biomechanics, and the migration of nestin+-BMSCs, detected by immunofluorescence staining. In vitro, nestin+ BMSCs were sorted and stimulated by tensile force to study the mechanisms of primary cilium-mediated mechanosensitive basis.RESULTS:
Mechanical stimulation (MS) accelerated the recruitment of nestin+-BMSCs and promoted osteogenic and chondrogenic capacity. Histological, imaging and biomechanical results showed that the BTI healing quality of the IFT88+/+, MS group was better than that of the other groups. After the conditionally knockout IFT88 in nestin+-BMSCs, the repair ability of the BTI was obviously deteriorated, even though mechanical stimulation did not increase significantly (IFT88-/-, MS group). In vitro results showed the tensile loading enhanced the proliferation, migration and osteogenic or chondrogenic gene expression of nestin+-BMSCs with normal cilia. On the other hand, osteogenesis and chondrogenic expression were significantly decreased after inhibiting actin- Hippo/YAP pathway components.CONCLUSION:
The primary cilia mediated mechanical stimulation regulated osteogenic and chondrogenic differentiation potential of nestin+-BMSCs through the actin- Hippo/YAP pathway, and then promoted the BTI healing process.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Adv Res
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Egipto