Compared to other vertebrates,the regenerative capacity of appendages in mammals is very limited.Deer antlers are an exception and can fully regenerate annually in postnatal mammals.This process is initiated by the an...Compared to other vertebrates,the regenerative capacity of appendages in mammals is very limited.Deer antlers are an exception and can fully regenerate annually in postnatal mammals.This 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 vitro.Thus,AnSCs were defined as MSCs,but with partial ESC attributes.Near-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 rats.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.展开更多
Deer antlers are the only known mammalian organ that,once lost,can fully grow back naturally.Hence,the antler offers a unique opportunity to learn how nature has solved the problem of mammalian epimorphic regeneration...Deer antlers are the only known mammalian organ that,once lost,can fully grow back naturally.Hence,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 limb.Surprisingly,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 mammals.Common 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 partner.The 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 regeneration.Due to absence of such an interactive partner,the CCC of a mouse/rat digit/limb stump becomes involuted gradually.Based 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 together.In so doing partial regeneration of the limb stump occurred.In 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.展开更多
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 w...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.展开更多
文摘Compared to other vertebrates,the regenerative capacity of appendages in mammals is very limited.Deer antlers are an exception and can fully regenerate annually in postnatal mammals.This 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 vitro.Thus,AnSCs were defined as MSCs,but with partial ESC attributes.Near-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 rats.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.
基金supported by National Natural Science Foundation of China(Regional Joint Funds,No.U20A20403).
文摘Deer antlers are the only known mammalian organ that,once lost,can fully grow back naturally.Hence,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 limb.Surprisingly,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 mammals.Common 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 partner.The 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 regeneration.Due to absence of such an interactive partner,the CCC of a mouse/rat digit/limb stump becomes involuted gradually.Based 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 together.In so doing partial regeneration of the limb stump occurred.In 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.
基金supported by the National Natural Science Foundation of China(No.81473314)
文摘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.
