Research On The Role Of PDK1 Gene In Maintaining The Stability Of Myotendinous Junction In Mice

Tendon injury is a common disease in clinical research.Due to the low density of tenocytes and the lack of blood vessels,the healing process after the injury is slow.At present,the research on the tendon tissue is still on the treatment method.There is a lack of research on the deep molecular mechanism of tendon.Phosphoinositide-Dependent Kinase 1(PDK1)is a kind of serine-threonine kinase,it belongs to the AGC kinase family.It can phosphorylate members of the AGC kinase family,and the activated AGC Kinase family can further regulate the growth,metabolism,anti-apoptosis and other physiological processes of cells.PDK1 is also one of the PI3K/AKT signal pathway upstream regulatory factors.It can activate the AKT/PI3 K signaling pathway by activating the AKT through phosphorylating the threonine 308(T308).The action of mechanical strain will activate the PI3K/AKT signal pathway in tendon derived stem cells(TDSCs).And the inhibition of the AKT/PI3 K signaling pathway can weak the tendon-like differentiation of the tendon-derived stem cells.So,to study the impaction of the PDK1 gene on tendon directly,we built a conditional knockout mouse which its tendon tissue lacks the PDK1 gene.The results of the study showed that the loss of the PDK1 gene in the tendon tissue resulted in the thinning of the myotendinous junction(MTJ).The maximum tension of MTJ can be reduced,and it is easier to break under mechanical load.At the same time,due to the loss of the PDK1 gene,the proliferation and tendon-like differentiation ability of TDSCs is weakened,and there is a risk of osteogenic differentiation.In this experiment,conditional gene knockout mice were constructed to confirm that PDK1 gene maintained the stability of myotendinous junction in Achilles tendon.This experiment was carried out from the gene level to study the factors affecting tendon repair and regeneration and the molecular mechanism regulating tendon metabolism.It also provides a theoretical basis for the clinical treatment of tendon injury.