髓核細胞對外力刺激的反應

Abstract

非典型下背痛與椎間盤退化有極大關係，並與其內髓核細胞退化有關，透過探討髓核細胞核內p-ERK訊號以及鈣離子濃度調控來了解髓核細胞受外力刺激時的反應。發展出能夠即時觀察之超音波刺激壓力載台，能在壓力環境下給予超音波刺激，發現NP細胞為一對外力敏感的細胞，在壓力及超音波刺激下p-ERK訊號皆增強，且會增加Sox9表現量，而長時間的壓力刺激也會增加髓核細胞的第二型膠原蛋白製造。以超音波玻璃針尖刺激及快速壓力變化探討髓核細胞的鈣離子反應，超音波刺激會透過ASIC3及GPCR增加細胞內鈣離子濃度，而在動態壓力下，增壓及洩壓時NP細胞也都會有鈣離子的正調控。NP細胞在人體內因從事運動而受到脊椎變形產生椎間盤內壓變化，會透過鈣離子調控進而影響下游細胞訊號，然而無法促進NP細胞增生，但能夠維持其生理功能，分泌細胞外基質，使椎間盤維持於健康狀態。椎間盤退化患者若無法從事運動，超音波治療可能扮演著提供相同刺激之工具，透過不同鈣離子及細胞因子調控路徑，促進NP生理功能，可能減緩椎間盤退化情形，維持椎間盤健康條件。

Ultrasound therapy were used as treatment to atypical low back pain and have been reported effective of patients’ chef complaint, while the mechanism still remains unknown. We investigate the nucleus pulposus cells’ intracellular calcium response and phosphorylation of ERK(p-ERK) to external mechanical force stimulation by hydrostatic pressure and ultrasound-micropipette. NP cells p-ERK was increased and highly translocated into nucleus after pressurized and ultrasonic stimuli. With ultrasound-micropipette investigation, which offering acoustic pressure and acoustic streaming stimuli, intracellular calcium was upregulated through ASIC3 and GPCR. Also, pressure change elevated calcium concentration, whether pressurizing or relief. Hence, we consider exercise could maintain intervertebral disc health with p-ERK activated through calcium signal pathway. Moreover, ultrasound therapy would utilize the high mechanosensitivity of NP to provide similar effect of exercises to NP to retards degeneration of intervertebral disc potentially