ZDHHC16 restrains osteogenic differentiation of bone marrow mesenchymal stem cells by inhibiting phosphorylation of CREB.
ZDHHC16 restrains osteogenic differentiation of bone marrow mesenchymal stem cells by inhibiting phosphorylation of CREB.
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DOI：
10.1016/j.heliyon.2022.e12788
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发表时间：
2023-01
期刊：
影响因子：
4
通讯作者：
Zhang, Chao
中科院分区：
文献类型：
--
作者：
Li, Zhiwei;Cheng, Yuan;Jin, Xiangyun;Liu, Shenghe;Zhang, Chao
人骨髓间充质干细胞（hBMSCs）的成骨作用在骨折愈合中起着关键作用。成骨分化受多种翻译后修饰的调控，但蛋白质棕榈酰化在成骨中的作用仍不清楚。本研究采用hBMSCs的成骨分化诱导。采用RT-PCR和免疫印迹法检测成骨诱导标志基因。采用碱性磷酸酶（ALP）活性测定、ALP染色及茜素红染色等方法检测hBMSCs的成骨能力。采用信号转导通路报告基因芯片、免疫共沉淀和WB等方法研究其分子机制。使用小鼠骨折模型来验证ZDHHC抑制剂的体内功能。我们发现棕榈酸抑制hBMSCs中Runx 2 mRNA的表达，并将ZDHHC 16鉴定为潜在的靶棕榈酰酰基转移酶。此外，ZDHHC 16在成骨诱导过程中减少。接下来，我们通过ZDHHC 16在hBMSCs成骨过程中的敲低或过表达证实了ZDHHC 16的抑制功能。此外，我们证明ZDHHC 16抑制CREB的磷酸化，从而通过增强CREB的棕榈酰化来抑制hBMSC的成骨。在小鼠股骨骨折模型中，我们发现ZDHHCs的一般抑制剂2-BP在体内促进骨折愈合。因此，我们阐明了ZDHHC 16在成骨分化过程中的抑制功能。总的来说，这些发现突出了ZDHHC 16在骨生成中的抑制功能，作为骨折愈合的潜在治疗方法。
The osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) plays a critical role in fracture healing. Osteogenic differentiation is regulated by a variety of post-translational modifications, but the function of protein palmitoylation in osteogenesis remains largely unknown. Osteogenic differentiation induction of hBMSCs was used in this study. RT‒qPCR and immunoblotting assays (WB) were used to test marker genes of osteogenic induction. Alkaline phosphatase (ALP) activity, ALP staining and Alizarin red staining were performed to evaluate osteogenesis of hBMSCs. Signal finder pathway reporter array, co-immunoprecipitation and WB were applied to elucidate the molecular mechanism. A mouse fracture model was used to verify the in vivo function of the ZDHHC inhibitor. We revealed that palmitic acid inhibited Runx2 mRNA expression in hBMSCs and identified ZDHHC16 as a potential target palmitoyl acyltransferase. In addition, ZDHHC16 decreased during osteogenic induction. Next, we confirmed the inhibitory function of ZDHHC16 by its knockdown or overexpression during osteogenesis of hBMSCs. Moreover, we illustrated that ZDHHC16 inhibited the phosphorylation of CREB, thus inhibiting osteogenesis of hBMSCs by enhancing the palmitoylation of CREB. With a mouse femur fracture model, we found that 2-BP, a general inhibitor of ZDHHCs, promoted fracture healing in vivo. Thus, we clarified the inhibitory function of ZDHHC16 during osteogenic differentiation. Collectively, these findings highlight the inhibitory function of ZDHHC16 in osteogenesis as a potential therapy method for fracture healing.
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影响因子：
5.2
作者：
Granero-Molto, Froilan;Myers, Timothy J.;Weis, Jared A.;Longobardi, Lara;Li, Tieshi;Yan, Yun;Case, Natasha;Rubin, Janet;Spagnoli, Anna
通讯作者：
Spagnoli, Anna
DOI：
10.1007/978-1-4939-9532-5_16
发表时间：
2019-01-01
期刊：
PROTEIN LIPIDATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Blanc, Mathieu;David, Fabrice P. A.;van der Goot, F. Gisou
通讯作者：
van der Goot, F. Gisou
DOI：
10.26355/eurrev_201712_13990
发表时间：
2017-12-01
影响因子：
3.3
作者：
Dong, C. -H.;Deng, Y. -S.;Zhen, P.
通讯作者：
Zhen, P.
DOI：
10.1038/nrrheum.2014.164
发表时间：
2015-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Fiddes IT;Lodewijk GA;Mooring M;Bosworth CM;Ewing AD;Mantalas GL;Novak AM;van den Bout A;Bishara A;Rosenkrantz JL;Lorig-Roach R;Field AR;Haeussler M;Russo L;Bhaduri A;Nowakowski TJ;Pollen AA;Dougherty ML;Nuttle X;Addor MC;Zwolinski S;Katzman S;Kriegstein A;Eichler EE;Salama SR;Jacobs FMJ;Haussler D
通讯作者：
Haussler D