Abstract
BackgroundDeer antlers are the only known mammalian organ with vascularized cartilage that can completely regenerate. Antlers are of real significance as a model of mammalian stem cell-based regeneration with particular relevance to the fields of chondrogenesis, angiogenesis, and regenerative medicine. Recent research found that thymosin beta 10 (TMSB10) is highly expressed in the growth centers of growing antlers. The present study reports here the expression, functions, and molecular interactions of deer TMSB10.MethodsThe TMSB10 expression level in both tissue and cells in the antler growth center was measured. The effects of both exogenous (synthetic protein) and endogenous deer TMSB10 (lentivirus-based overexpression) on antlerogenic periosteal cells (APCs; nonactivated antler stem cells with no basal expression of TMSB10) and human umbilical vein endothelial cells (HUVECs; endothelial cells with no basal expression of TMSB10) were evaluated to determine whether TMSB10 functions on chondrogenesis and angiogenesis. Differences in deer and human TMSB10 in angiogenesis and molecular structure were determined using animal models and molecular dynamics simulation, respectively. The molecular mechanisms underlying deer TMSB10 in promoting angiogenesis were also explored.ResultsDeer TMSB10 was identified as a novel proangiogenic factor both in vitro and in vivo. Immunohistochemistry revealed that TMSB10 was widely expressed in the antler growth center in situ, with the highest expression in the reserve mesenchyme, precartilage, and transitional zones. Western blot analysis using deer cell lines further supports this result. Both exogenous and endogenous deer TMSB10 significantly decreased proliferation of APCs (P < 0.05), while increasing the proliferation of HUVECs (P < 0.05). Moreover, deer TMSB10 enhanced chondrogenesis in micromass cultures and nerve growth as assessed using a dorsal root ganglion model (P < 0.05). Deer TMSB10 was proangiogenic using models of chicken chorioallantoic membrane, tube formation, and aortic arch assay. At the molecular level, endogenous deer TMSB10 elevated the expression of vascular endothelial growth factor (VEGF), VEGF-B, VEGF-C, and VEGF-D, and VEGFR2 and VEGFR3 in HUVECs (P < 0.05).ConclusionsDeer TMSB10, in contrast to its human counterpart, was identified as a novel stimulating factor for angiogenesis, cartilage formation, and nerve growth, which is understandable given that deer antlers (as the arguably fastest mammalian growing tissue) may require this extra boost during a period of rapid growth and regeneration.
Highlights
Deer antlers are the only known mammalian organ with vascularized cartilage that can completely regenerate
Our results provide the first evidence that deer thymosin beta 10 (TMSB10) is proangiogenic, and its expression may contribute significantly to the blood vessel growth required during rapid antler regeneration
Reagents and antibody Recombinant vascular endothelial growth factor (VEGF; 100–20), recombinant nerve growth factor (β-NGF; 450–01), recombinant human transforming growth factor (TGFβ1; 100–21), and recombinant human hepatocyte growth factor (HGF; 100-39H) were purchased from Peprotech Inc. (USA); basic fibroblast growth factor was purchased from Dalian Meilunbio (China); dexamethasone (D1756), L-ascorbic acid 2-phosphate (A4403-100MG), and L-proline (P0380-10MG) was purchased from Sigma (USA); and ITS Premix Universal Culture Supplement was purchased from Corning (USA, 354351)
Summary
Deer antlers are the only known mammalian organ with vascularized cartilage that can completely regenerate. Antlers are of real significance as a model of mammalian stem cell-based regeneration with particular relevance to the fields of chondrogenesis, angiogenesis, and regenerative medicine. The ultimate goal of regeneration research using model animals and/or organs such as antlers is to learn whether they can be used as a suitable model for regenerative medicine. Previous studies show that annual antler renewal is a stem cell-based epimorphic process driven by stem cells resident in the pedicle periosteum (PP). Better understanding of the mechanisms of antler regeneration would undoubtedly contribute to the field of regenerative medicine, as well as provide potential application for treating some clinical diseases such as bone defects, osteonecrosis of the femoral head (ONFH), and bone fractures [5,6,7,8]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.