Dataset Information

Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway.

ABSTRACT: Deer antler preparations have been used to strengthen bones for centuries. It is particularly rich in collagen type I. This study aimed to unravel part of the purported bioremedial effect of Sika deer antler collagen type I (SDA-Col I) on bone marrow mesenchymal stem cells. The results suggest that SDA-Col I might be used to promote and regulate osteoblast proliferation and differentiation. SDA-Col I might potentially provide the basis for novel therapeutic strategies in the treatment of bone injury and/or in scaffolds for bone replacement strategies. Finally, isolation of SDA-Col I from deer antler represents a renewable, green, and uncomplicated way to obtain a biomedically valuable therapeutic.

SUBMITTER: Li N

PROVIDER: S-EPMC4809101 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway.

Li Na N Zhang Min M Drummen Gregor P C GP Zhao Yu Y Tan Yin Fen YF Luo Su S Qu Xiao Bo XB

Evidence-based complementary and alternative medicine : eCAM 20160104

Deer antler preparations have been used to strengthen bones for centuries. It is particularly rich in collagen type I. This study aimed to unravel part of the purported bioremedial effect of Sika deer antler collagen type I (SDA-Col I) on bone marrow mesenchymal stem cells. The results suggest that SDA-Col I might be used to promote and regulate osteoblast proliferation and differentiation. SDA-Col I might potentially provide the basis for novel therapeutic strategies in the treatment of bone in ...[more]

PMID: 27066099

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Project description:Antler is a special bone tissue that has the ability to regenerate completely periodically. It is the fastest growing bone in the animal kingdom. Antler provides a valuable research model for bone growth and mineralization. Antler grows longitudinally by endochondral ossification with their growth center located in its tip. Many scholars have carried out detailed studies on morphology and gene expression of antler tip. However, few scholars have analyzed the protein expression patterns of antler tip at different development stages. This study used label-free proteomics approach to analyze the protein expression dynamics of the antler tip in six developmental periods (15, 25, 45, 65, 100 and 130 days after the previous antler cast) and costal cartilage. In result, 2052 proteins were confidently quantified, including 1937 antler proteins and 1044 costal cartilage proteins. Moreover, 913 antler core proteins and 132 antler-special proteins were obtained. Besides, the stages special proteins and differentially expressed proteins (DEPs) in different development stages were analyzed. A total of 875 DEPs were determined by one-way AVOVA. It is found that the growth period (15, 25, 45 and 65 days) showed more up-regulated protein including several chondrogenesis-associated proteins (collagen types II, collagen types XI, HAPLN1, PAPSS1 and PAPSS2). In ossification stages, the up-regulated proteins related with lysosome (CTSD, CTSB, MMP9, CAII) indicated that the antler has higher bone remodeling activity. Given the up-regulated expression of immune-related molecules (S100A7, CATHL7, LTF, AZU1, ELANE and MPO), we speculate that the local immune system may contribute to the ossification of antler tip. In conclusion, proteomics technology was used to deeply analyze the protein expression patterns of antler at different development stages. This provides a strong support for the research on the molecular regulation mechanism of rapid growth and ossification of velvet antler.

Project description:Chordin-like 1 (CHRDL1) is a secreted glycoprotein with repeated cysteine-rich domains, which can bind to BMPs family ligands. Although it has been reported to play important roles in several systems, the exact roles of CHRDL1 on human bone mesenchymal stem cells (hBMSCs) osteogenesis remain to be explored. The present study aimed to investigate the roles of CHRDL1 on the osteogenic differentiation of hBMSCs and the underlying molecular mechanisms. We found that CHRDL1 was upregulated during hBMSCs osteogenesis, and rhBMP-4 administration could enhance CHRDL1 mRNA expression in a dose and time dependent manner. Knockdown of CHRDL1 did not affect hBMSCs proliferation, but inhibited the BMP-4-dependent osteogenic differentiation, showing decreased mRNA expression levels of osteogenic markers and reduced mineralization. On the contrary, overexpression of CHRDL1 enhanced BMP-4 induced osteogenic differentiation of hBMSCs. Moreover, in vivo experiments by transplanting CHRDL1 gene modified hBMSCs into nude mice defective femur models displayed higher new bone formation in CHRDL1 overexpression groups, but lower new bone formation in CHRDL1 knockdown groups, compared with control groups. In consistent with the bone formation rate, there were increased CHRDL1 protein expression in new bone formation regions of defective femur in CHRDL1 overexpression groups, while reduced CHRDL1 protein expression in CHRDL1 knockdown groups compared with control groups. These indicate that CHRDL1 can promote osteoblast differentiation in vivo. Furthermore, the mechanisms study showed that CHRDL1 improved BMP-4 induced phosphorylation of SMAD1/5/9 during osteogenic differentiation of hBMSCs. Besides, promotion of osteogenic differentiation and the activation of SMAD phosphorylation by CHRDL1 can be blocked by BMP receptor type I inhibitor LDN-193189. In conclusion, our results suggested that CHRDL1 can promote hBMSCs osteogenic differentiation through enhancing the activation of BMP-4-SMAD1/5/9 pathway.

Project description:BackgroundWith the unprecedented rapid growth rate (up to 2.75 cm/day), velvet antler is an invaluable model for the identification of potent growth factors and signaling networks for extremely fast growing tissues, mainly cartilage. Antler growth center (AGC) locates in its tip and consists of five tissue layers: reserve mesenchyme (RM), precartilage (PC), transition zone (TZ), cartilage (CA) and mineralized cartilage (MC). The aim of this study was to investigate the transcription dynamics in the AGC using RNA-seq technology.ResultsFive tissue layers in the AGC were collected from three 3-year-old male sika deer using our previously reported sampling method (morphologically distinguishable). After sequencing (15 samples; triplicates/tissue layer), we assembled a reference transcriptome de novo and used RNA-seq to measure gene expression profiles across these five layers. Nine differentially expressed genes (DEGs) were selected from our data and subsequently verified using qRT-PCR. The results showed a high consistency with the RNA-seq results (R2 = 0.80). Nine modules were constructed based on co-expression network analysis, and these modules contained 370 hub genes. These genes were found to be mainly involved in mesenchymal progenitor cell proliferation, chondrogenesis, osteogenesis and angiogenesis. Combination of our own results with the previously published reports, we found that Wnt signaling likely plays a key role not only in stimulating the antler stem cells or their immediate progeny, but also in promoting chondrogenesis and osteogenesis during antler development.ConclusionWe have successfully assembled a reference transcriptome, generated gene expression profiling across the five tissue layers in the AGC, and identified nine co-expressed modules that contain 370 hub genes and genes predorminantly expressed in and highly relevant to each tissue layer. We believe our findings have laid the foundation for the identification of novel genes for rapid proliferation and chondrogenic differentiation of antler cells.

Dataset Information

Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway.

Publications

Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway.

Similar Datasets

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