Xuesong Han1, Lin Guo2, Fuyou Wang3, Qingsheng Zhu4, Liu Yang3. 1. Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi׳an 710032, China; Department of Orthopedics, Fuzhou General Hospital of Nanjing, Command, PLA, Fuzhou 350025, China. 2. Center of Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China. Electronic address: guolin6212@163.com. 3. Center of Joint Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China. 4. Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi׳an 710032, China. Electronic address: zhuqsh@fmmu.edu.cn.
Abstract
BACKGROUND: Fibrochondrocytes are involved in entheses repair, but their response to mechanical strain (MS) is ill known. OBJECTIVE: To determine if parathyroid hormone-related protein (PTHrP) expression in fibrochondrocytes from fibrocartilaginous entheses is modulated by MS, and to further observe the regulatory effects of human (h) PTHrP on fibrochondrocyte differentiation. METHODS: Fibrochondrocytes from fibrocartilaginous entheses of Guizhou miniature pig׳s Achilles tendon were submitted or not to MS (4%, 8% or 12% cyclic tensile strain; 1 Hz). Fibrochondrocytes were also exposed to: cyclopamine (Indian hedgehog (Ihh) inhibitor) (10 μM), hPTHrP (10 nM) or cyclopamine/hPTHrP (cyclopamine 10 uM+hPTHrP 10 nM). Types I, II and X collagen and PTHrP expressions were measured by real-time RT-PCR and Western blot. RESULT: Under 4% strain load for 12 h, types I and II collagen mRNA expressions were increased (+324% and +659%, P<0.001), while type X collagen was decreased (-89%, P<0.001). At 12%, types I and II collagen mRNA expressions were decreased (-62% and -62%, P<0.001), while type X collagen was increased (+375%, P<0.05). Under 4% strain load, PTHrP mRNA expression was increased in relation with strain duration (from 3 to 12 h: +168%, P<0.001), while at 12%, PTHrP expression decreased with time (from 3 to 12 h: -81%, P<0.001). Using cyclopamine for 24 h, PTHrP mRNA expression was significantly decreased (-88%, P<0.05), types I and II collagen were decreased (-90% and -82%, P<0.001), and type X collagen was increased (+261%, P<0.001). CONCLUSIONS: Dynamic MS modulate PTHrP expressions. Thus, PTHrP might play an important role in fibrochondrocyte differentiation, indirectly revealing a role in entheses׳ formation and repair.
BACKGROUND: Fibrochondrocytes are involved in entheses repair, but their response to mechanical strain (MS) is ill known. OBJECTIVE: To determine if parathyroid hormone-related protein (PTHrP) expression in fibrochondrocytes from fibrocartilaginous entheses is modulated by MS, and to further observe the regulatory effects of human (h) PTHrP on fibrochondrocyte differentiation. METHODS: Fibrochondrocytes from fibrocartilaginous entheses of Guizhou miniature pig׳s Achilles tendon were submitted or not to MS (4%, 8% or 12% cyclic tensile strain; 1 Hz). Fibrochondrocytes were also exposed to: cyclopamine (Indian hedgehog (Ihh) inhibitor) (10 μM), hPTHrP (10 nM) or cyclopamine/hPTHrP (cyclopamine 10 uM+hPTHrP 10 nM). Types I, II and X collagen and PTHrP expressions were measured by real-time RT-PCR and Western blot. RESULT: Under 4% strain load for 12 h, types I and II collagen mRNA expressions were increased (+324% and +659%, P<0.001), while type X collagen was decreased (-89%, P<0.001). At 12%, types I and II collagen mRNA expressions were decreased (-62% and -62%, P<0.001), while type X collagen was increased (+375%, P<0.05). Under 4% strain load, PTHrP mRNA expression was increased in relation with strain duration (from 3 to 12 h: +168%, P<0.001), while at 12%, PTHrP expression decreased with time (from 3 to 12 h: -81%, P<0.001). Using cyclopamine for 24 h, PTHrP mRNA expression was significantly decreased (-88%, P<0.05), types I and II collagen were decreased (-90% and -82%, P<0.001), and type X collagen was increased (+261%, P<0.001). CONCLUSIONS: Dynamic MS modulate PTHrP expressions. Thus, PTHrP might play an important role in fibrochondrocyte differentiation, indirectly revealing a role in entheses׳ formation and repair.
Authors: Francesco Oliva; Emanuela Marsilio; Giovanni Asparago; Alessio Giai Via; Carlo Biz; Johnny Padulo; Marco Spoliti; Calogero Foti; Gabriella Oliva; Stefania Mannarini; Alessandro Alberto Rossi; Pietro Ruggieri; Nicola Maffulli Journal: J Clin Med Date: 2022-06-27 Impact factor: 4.964