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Deer antler renewal gives insights into mammalian epimorphic regeneration

Cell Regeneration 2023年第1期12卷 147-162页

作者： Chunyi Li Institute of antler Science and Product Technology Changchun Sci-Tech UniversityChangchun 130600China Jilin Provincial Key Laboratory of Deer antler Biology Changchun 130600China College of Chinese Medicinal Materials Jilin Agricultural UniversityChangchun 130000China

Deer antlers are the only known mammalian organ that,once lost,can fully grow back ***,the antler offers a unique opportunity to learn how nature has solved the problem of mammalian epimorphic regeneration(EpR).Comprehensive comparisons amongst different types of EpR reveal that antler renewal is fundamentally different from that in lower vertebrates such as regeneration of the newt ***,antler renewal is comparable to wound healing over a stump of regeneration-incompetent digit/limb,bone fracture repair,and to a lesser extent to digit tip regeneration in *** to all these mammalian cases of reaction to the amputation/mechanical trauma is the response of the periosteal cells at the distal end/injury site with formation of a circumferential cartilaginous callus(CCC).Interestingly,whether the CCC can proceed to the next stage to transform to a blastema fully depends on the presence of an interactive *** actual form of the partner can vary in different cases with the nail organ in digit tip EpR,the opposing callus in bone fracture repair,and the closely associated enveloping skin in antler *** to absence of such an interactive partner,the CCC of a mouse/rat digit/limb stump becomes involuted *** on these discoveries,we created an interactive partner for the rat digit/limb stump through surgically removal of the interposing layers of loose connective tissue and muscle between the resultant CCC and the enveloping skin after amputation and by forcefully bonding two tissue types tightly *** so doing partial regeneration of the limb stump *** summary,if EpR in humans is to be realized,then I envisage that it would be more likely in a manner akin to antler regeneration rather to that of lower vertebrates such as newt limbs.

关键词： antler antler regeneration Epimorphic regeneration Digit/limb stump Bone fracture Callus

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Single-cell transcriptome reveals core cell populations and androgen-RXFP2 axis involved in deer antler full regeneration

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Cell Regeneration 2022年第1期11卷 449-467页

作者： Hengxing Ba Xin Wang Datao Wang Jing Ren Zhen Wang Hai-Xi Sun Pengfei Hu Guokun Zhang Shengnan Wang Chao Ma Yusu Wang Enpeng Wang Liang Chen Tianbin Liu Ying Gu Chunyi Li Institute of antler Science and Product Technology Changchun Sci-Tech UniversityChangchun 130600China Jilin Provincial Key Laboratory of Deer antler Biology Changchun 130600China BGI-Shenzhen Shenzhen 518083GuangdongChina Hubei Key Laboratory of Cell Homeostasis College of Life SciencesRNA InstituteWuhan UniversityWuhanChina Institute of Special Wild Economic Animals and Plants Chinese Academy of Agricultural Sciences130112ChangchunChina Jilin Ginseng Academy Changchun University of Chinese MedicineChangchun 130117China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Guangdong Provincial Key Laboratory of Genome Read and Write BGI-ShenzhenShenzhen 518120GuangdongChina College of Chinese Medicinal Materials Jilin Agricultural UniversityChangchun 130118China

Deer antlers constitute a unique mammalian model for the study of both organ formation in postnatal life and annual full *** studies revealed that these events are achieved through the proliferation and differentiation of antlerogenic periosteum(AP)cells and pedicle periosteum(PP)cells,*** the cells resident in the AP and the PP possess stem cell attributes,both antler generation and regeneration are stem cell-based ***,the cell composition of each tissue type and molecular events underlying antler development remain poorly ***,we took the approach of single-cell RNA sequencing(scRNA-Seq)and identified eight cell types(mainly THY1^(+)cells,progenitor cells,and osteochondroblasts)and three core subclusters of the THY1^(+)cells(SC2,SC3,and SC4).Endothelial and mural cells each are heterogeneous at transcriptional *** was the proliferation of progenitor,mural,and endothelial cells in the activated antler-lineage-specific tissues that drove the rapid formation of the *** detected the differences in the initial differentiation process between antler generation and regeneration using pseudotime trajectory *** may be due to the difference in the degree of stemness of the AP-THY1+and PP-THY1^(+)*** further found that androgen-RXFP2 axis may be involved in triggering initial antler full *** deciphering the cell composition for these antler tissue types will open up new avenues for elucidating the mechanism underlying antler full renewal in specific and regenerative medicine in general.

关键词： antler THY1+cell Generation Regeneration Core cell population Androgen-RXFP2 axis Single cell sequencing

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antler stem cells and their potential in wound healing and bone regeneration

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World Journal of Stem Cells 2021年第8期13卷 1049-1057页

作者： Wei Zhang Chang-Hong Ke Hai-Hua Guo Li Xiao Medical Imaging Center The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou 510080Guangdong ProvinceChina Research&Development Center YZ Health-tech Inc.Zhuhai 519000Guangdong ProvinceChina School of Pharmacy Jinan UniversityGuangzhou 510080Guangdong ProvinceChina Institute of Biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhou 510006Guangdong ProvinceChina Guangdong Laboratory Animals Monitoring Institute and Guangdong Provincial Key Laboratory of Laboratory Animals Guangzhou 510080Guangdong ProvinceChina

Compared to other vertebrates,the regenerative capacity of appendages in mammals is very *** antlers are an exception and can fully regenerate annually in postnatal *** process is initiated by the antler stem cells(AnSCs).AnSCs can be divided into three types:(1)antlerogenic periosteum cells(for initial pedicle and first antler formation);(2)Pedicle periosteum cells(for annual antler regeneration);and(3)Reserve mesenchyme cells(RMCs)(for rapid antler growth).Previous studies have demonstrated that AnSCs express both classic mesenchymal stem cells(MSCs)and embryonic stem cells(ESCs),and are able to differentiate into multiple cell types in ***,AnSCs were defined as MSCs,but with partial ESC ***-perfect generative wound healing can naturally occur in deer,and wound healing can be achieved by the direct injection of AnSCs or topical application of conditioned medium of AnSCs in *** addition,in rabbits,the use of both implants with AnSCs and cell-free preparations derived from AnSCs can stimulate osteogenesis and repair defects of bone.A more comprehensive understanding of AnSCs will lay the foundation for developing an effective clinical therapy for wound healing and bone repair.

关键词： antler Stem cells Regeneration Wound healing Bone repair

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Pilose antler aqueous extract promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells by stimulating the BMP-2/Smad1, 5/Runx2 signaling pathway

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Chinese Journal of Natural Medicines 2019年第10期17卷 756-767页

作者： REN Cong GONG Wei LI Feng XIE Ming School of Pharmacy L iaoning University of Traditional Chinese MedicineDalian 116600China Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Shenyang 110032China

Peptides from Pilose antler aqueous extract(PAAE) have been shown to stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells(BMSCs). However, the underlying molecular mechanisms are not well understood. Here, PAAE was isolated and purified to explore the molecular mechanisms underlying PAAE’s effects on BMSCs as well as its osteoprotective effects in ovariectomized rats. Our results showed that PAAE promoted proliferation and differentiation of BMSCs to become osteoblasts by enhancing ALP activity and increasing extracellular matrix mineralization. The trabecular microarchitecture of ovariectomized rats was also found to be protected by PAAE. Quantitative reverse transcription-polymerase chain reaction(Quantitative RT-PCR) results suggest that PAAE also increased the expression of osteogenic markers including, alkaline phosphatase(ALP), runt-related transcription factor 2(Runx2), osteocalcin(OCN), bone morphogenetic protein-2(BMP-2), and collagen I(COL-I). Immunoblotting results indicated that PAAE upregulated the levels of BMP-2 and Runx2 and was associated with Smad1/5 phosphorylation. PAAE A at the concentration of 200μg·mL^-1 showed the strongest effect on proliferation and osteogenic differentiation of BMSCs after 48 h. Using matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS), we identified the molecular weight of PAAE A and found that it is less than 3000 Da and showed several significant peaks. In conclusion, PAAE activates the BMP-2/Smad1, 5/Runx2 pathway to induce osteoblastic differentiation and mineralization in BMSCs and can inhibit OVX-induced bone loss. These mechanisms are likely responsible for its therapeutic effect on postmenopausal osteoporosis.

关键词： Pilose antler Postmenopausal osteoporosis Bone marrow mesenchymal stem cells BMP-2/Smad1,5/Runx2 signaling pathway

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Therapeutic effects of velvet antler polypeptides on hepatic fibrosis in rats

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中国药理学与毒理学杂志 2015年第S1期29卷 56-57页

作者： Leng-xinDUAN Cai-eWANG Ji-leXIN Yi-mengDUAN Jian-gangWANG Medical College Henan University of Science and Technology Luoyang 471003 China Pharmacy College Jilin University Changchun 130021 China

OBJECTIVE To explore the therapeutic effects and underlying mechanisms of velvet antler polypeptides(VVAPs)in CCl4-induced experimental hepatic fibrosis in *** Anti-hepatic fibrosis properties of VAPs were tested by Subcutaneous injection(SC)into male Wistar rats of CCl4- induced experimental hepatic *** SC injections for 45 consecutive days at doses of 5mg·kg-1(low dose,VAPsL),10mg·kg-1(mid-dose,VAPsM)and 20mg·kg-1(high-dose,VAPsH),the rats were sacrificed and the various indicators were evaluated and *** hepatic cells degeneration and necrosis,inflammatory infiltration and levels of serum enzymes to assess treatment of VAPs;The expression levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),MDA,and hydroxyproline(HYP)in liver tissue were analyzed;RT-PCR analysis was carried out to detect the expression levels of matrix metalloproteinases2(MMP-2)and tissue inhibitor of metalloproteinases 1(TIMP-1)in liver *** VAPs has obvious anti-hepatic fibrosis *** swelling,fatty degeneration was significantly reduced,reducing infiltration of inflammatory *** of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)decreased significantly,reduction of hyaluronic acid(HA)and laminin(LN)obviously,at the same time,the content of total protein and albumin increased significantly in *** of SOD and GSH-Px was significantly raised and the content of MDA and HYP was reduced significantly in liver *** levels of MMP-2and TIMP-1 mRNA in liver were decreased *** improvements were more significant in high-dos and mid-dose groups(P<0.05 or P<0.01 vs model group).CONCLUSION These findings suggest VAPs can significant treat the hepatic fibrosis,which may be due to protect liver cells and improve liver functions by hydroxyl radical scavenging activity and great effect of antioxidation,and decrease the gene expression of MMP-2,improving exist-environment of liver ce

关键词： velvet antler polypeptide hepatic fibrosis oxidati

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