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One or more keywords matched the following properties of He, Tong-Chuan

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keywords Mesenchymal Stem Cells
overview I direct the Molecular Oncology Laboratory in the Department of Orthopaedic Surgery and Rehabilitation Medicine. Our lab consists of a dynamic group of basic science investigators and physician scientists, who have diverse expertise and a broad range of research interests. Our shared long-term objective is to better understand the molecular pathogenesis of bone and musculoskeletal diseases and to translate basic discoveries into potential therapies and/or preventive measures in clinical settings. Specifically, we focus on the following areas: LINEAGE COMMITMENT AND TERMINAL DIFFERENTIATION OF MESENCHYMAL STEM CELLS (MSCS) Multipotency of MSCs MSCs are pluripotent and capable of differentiating into osteogenic, chondrogenic, myogenic or adipogenic lineage. Understanding the molecular mechanisms of bone formation is pivotal for studying the pathogenesis of bone diseases. We are interested in elucidating the molecular mechanisms through which regulate the proliferation and differentiation of osteoblasts, chondrocytes, and adipocytes. Both Wnt/beta-catenin and bone morphogenetic proteins (BMPs) have been considered as important regulators of osteogenic differentiation of mesenchymal stem cells. We are investigating the biological functions of BMPs and Wnt/beta-catenin signaling in regulating the osteoblast differentiation of MSCs. We have therefore conducted a comprehensive analysis of BMP and Wnt3A-induced osteoblast differentiation of MSCs. Our findings indicate that osteoblast differentiation is a well-regulated process in normal progenitor cells, while osteosarcoma cells are refractory to osteogenic differentiation signal. BMP-9 is one of the most potent regulators of osteogenic differentiation The bone-forming osteoblasts are derived from pluripotent bone marrow fibroblasts (a.k.a., MSCs). Although the molecular mechanisms underlying bone formation remain to be defined, BMPs seem to play an important role in osteoblast differentiation. At least 15 types of BMPs have been identified in mice and humans. However, the ability of BMPs to induce osteoblast differentiation of mesenchymal stem cells has not been comprehensively investigated, mostly due to the fact that recombinant proteins are either not biologically active or not available for all BMPs. Through a comprehensive analysis, we found that BMP2, BMP6, and BMP9 (to a much lesser extent, BMP4 and BMP7) exhibited the greatest ability to induce osteoblast differentiation, whereas BMP3 was shown to inhibit osteogenesis, both in vitro and in vivo. Our findings about BMP9 as one of the most potent inducers of osteoblast differentiation are novel and particularly intriguing because BMP9 is one of the least characterized BMPs and its functions are largely unknown. Thus, many questions regarding BMP9 signaling need to be answered: What are the type I and type II TGFbeta/BMP receptors involved in BMP9 binding? What Smads are required for BMP9 signaling? How are the downstream targets regulated by BMP9? More importantly, what are the roles of BMP9 during embryonic and/or skeletal development? We are interested in addressing these questions. Critical mediators of BMP-induced differentiation of MSCs We have identified several potentially important signaling mediators of BMP-induced osteogenic differentiation. These targets include the Inhibitors of DNA binding/Differentiation helix-loop-helix (a.k.a., Id proteins) and CTGF. Interestingly, both Ids and CTGF have been shown to overexpress in human tumors. Our findings suggest that Ids and CTGF may play an important role in promoting the proliferation of early osteoblast progenitor cells and that their expression must be down-regulated during the terminal differentiation of committed osteoblasts, suggesting that a balanced regulation of their expression may be critical to BMP-induced osteoblast lineage-specific differentiation of MSCs. We are currently dissecting the functional roles of the important downstream mediators in BMP-induced osteogenic signaling. We are also interested in identifying the molecular switches that control the lineage-specific differentiation of osteoblasts, chondrocytes, and adipocytes in MSCs. We are especially interested in understanding at what stage osteogenic BMPs (e.g., BMP2 or BMP9)-induced osteogenic and adipogenic differentiation diverges. What are the potential regulators that control this lineage divergence? It has been long postulated that a disrupted balance between osteogenesis and adipogenesis may cause musculoskeletal diseases, such as osteoporosis. Wnts regulate osteogenic differentiation of mesenchymal stem cells Our earlier studies demonstrated that Wnt/beta-catenin signaling is de-regulated in over 70% of human osteosarcoma. Recent studies also suggest that Wnt signaling may play an important role in regulating bone density, and one of the Wnt signaling antagonists Dkk1 may be implicated in the development of osteolytic lesion in multiple myeloma patients. We demonstrated that Wnt3A can induce the early osteogenic marker alkaline phosphatase in MSCs. Upon analyzing the gene expression profile of MSCs that were stimulated with Wnt3A, we found that three members of the CCN family, CCN1/Cyr61, CCN2/CTGF, and CCN5/WISP2, were among the most significantly up-regulated genes. Further studies demonstrate that CTGF is a mutual target of Wnt and BMP-9, and plays an important role in regulating osteogenic differentiation. However, more questions remain to be answered. We are currently investigating how osteogenic differentiation of MSCs is regulated by canonical and non-canonical Wnt signaling. MOLECULAR BASES OF BONE AND SOFT TISSUE SARCOMAS Sarcomas represent a heterogeneous group of malignant mesenchymal tumors with numerous histologic subtypes and complex cytogenetic abnormalities. Unlike other common solid tumors, sarcomas are relatively uncommon and their molecular pathogenesis, in general, are poorly understood. We mainly focus on understanding the molecular biology of primary bone tumor (a.k.a., osteosarcoma, OS). Osteosarcoma is the most common primary malignancy of bone, and is among the most common non-hematological primary tumors of bone in both children and adults. The peak incidence occurs in the second decade. With preoperative chemotherapy, the five-year survival rate of patients with non-metastatic tumors has improved significantly to approximately 60-70%. However, cases with local recurrence and/or pulmonary metastasis are usually less sensitive, if not resistant, to conventional chemotherapies. Several cytogenetic studies suggest that certain chromosomal regions may be amplified, rearranged, or deleted in some, but not all, human osteosarcomas. Unfortunately, the low incidence of this disease and the absence of any familial predisposition have complicated efforts to identify osteosarcoma-associated genes. Thus, we are taking a comprehensive approach to elucidate the molecular mechanisms underlying the development of osteosarcoma. Wnt/beta-catenin signaling in the development of human osteosarcoma Aberrant activation of Wnt/beta-catenin signaling by inactivating APC tumor suppressor or oncogenic activation of beta-catenin plays an important role in colorectal tumorigenesis. Oncogenic activation of beta-catenin has also been reported in several types of human solid tumors. We found that beta-catenin signaling is de-regulated in about 70% of human osteosarcoma without beta-catenin mutations. As in many other types of non-colon cancer, little is known about how Wnt/beta-catenin signaling pathway is activated. Therefore, we are interested in elucidating the upstream regulatory mechanisms that may underline of the beta-catenin signaling pathway. We are also interested in investigating the possible pathogenic role of beta-catenin deregulation in bone and soft tissue tumors. Furthermore, we are investigating the potential roles of EF-hand calcium-binding S100 proteins in osteosarcoma progression and the development of pulmonary metastasis. Clinically relevant osteosarcoma animal model In order to investigate the pathogenesis of human osteosarcoma, there is a great need to develop a clinically relevant animal model. We have developed such an orthotopic animal model of osteosarcoma using several human osteosarcoma lines. This clinically relevant model of human osteosarcoma provides varying degrees of tumor growth at the primary site and of metastatic potential. Thus, this orthotopic model is being used as a valuable tool to investigate factors that promote or inhibit osteosarcoma growth and/or metastasis. For instance, we are now using this model to investigate the roles of genes that are known to promote cell proliferation and inhibit differentiation, and genes that potentially promote or inhibit cancer metastasis. This orthotopic model can also be used to test anti-tumor small molecules or other targeted therapies. Osteosarcoma is a differentiation disease We believe that understanding the molecular events behind normal osteoblast differentiation of MSCs may provide important clues to osteosarcoma development. Stem cell differentiation and tumorigenesis share some strikingly similar characteristics. Both normal stem cells and cancer stem cells have the ability to self-renew. Although stem cells are often the target of genetic events that are necessary or sufficient for malignant transformation, in some cases restricted progenitors or even differentiated cells may become transformed. Thus, cancer stem cells may be derived from tissue-specific stem cells or progenitors, such as MSCs. Although cancer stem cells for osteosarcoma remain to be identified, OS cells indeed exhibit the characteristics of undifferentiated osteoblasts, and we have shown that differentiation-promoting agents can inhibit OS proliferation. Accordingly, we found that human osteosarcoma cells are in general refractory to osteogenic BMPs and exhibit no signs of terminal differentiation upon osteogenic BMP stimulation. Thus, we hypothesize that osteosarcoma development is caused by molecular/genetic disruptions of the osteogenic differentiation pathway. We are investigating and identifying the possible defects in osteogenic pathway, including the possible roles of the early target genes of BMP-induced osteoblast lineage-specific differentiation of MSCs. MOLECULAR BIOLOGY OF CANCER METASTASIS Cancer metastasis is an often overlooked and least understood problem. Metastasis is defined as the progressive growth of tumor cells at a site that is discontinuous from the primary tumor. Although not an efficient process, colonization at distant tissues by tumor cells represents the most dangerous attribute of cancer, because metastases, rather than primary tumors, are responsible for most cancer deaths. Metastatic cells are a subset of primary tumor cells that have acquired the ability to complete a multi-step metastatic cascade, including migration, dissemination, extravasation, and eventual proliferation at a discontinuous secondary site. Understanding the molecular biology of cancer metastasis may provide novel intervention strategies to control/contain metastatic lesions, and/or to improve the quality of life for the patients with these advanced diseases. Pulmonary metastasis of primary bone tumors Lung metastasis is the leading cause of OS mortality. Our orthotopic tumor model of human OS provides a unique opportunity for us to investigate the molecular events underlying osteosarcoma pulmonary metastasis. Using this model, we have conducted serial selections of highly metastatic human OS sublines, which were otherwise non-metastatic. Using microarray analysis, we have compared the gene expression profiles between these sublines and the parental lines in search for gene(s) that may cause or be associated with osteosarcoma metastasis. In an alternative approach, we are conducting functional selection assays, in which an RNAi library has been introduced into the non-metastatic or less metastatic human osteosarcoma cells to recover lung metastases and to identify potential metastasis suppressors of human osteosarcoma. Metastatic bone tumors Bone is one of the most frequently targeted organs for cancer metastasis, and bone is the most common site for distant relapse of most cancers. The bone microenvironment is unique among metastatic target tissues because it is subjected to continuous remodeling under the influence circulating hormones and local bone-derived factors. Interactions between the bone microenvironment and the cancer cells can give rise to osteolytic (bone resorbing) or osteoblastic (bone forming) metastasis. Osteolytic bone metastasis are characteristic for most malignancies, such as breast cancer and lung cancer, while osteoblastic metastasis is mostly associated with prostate cancer. We are investigating the molecular mechanisms through which the interactions between metastatic (breast and prostate) cancer cells and bone microenvironment are regulated. NOVEL THERAPEUTIC AND/OR PREVENTIVE STRATEGIES FOR BONE AND MUSCULOSKELETAL DISEASES The ultimate goal of biomedical research is to develop innovative diagnostic, therapeutic, and/or preventive strategies for human diseases. We are interested in developing innovative approaches for local or systemic delivery of therapeutic genes as effective treatment for bone and musculoskeletal diseases. We are investigating the use of osteogenic BMPs for bone regeneration, enhancing fracture healing, repairing segmental defects, promoting spinal fusion, and preventing implant wear particle-induced osteolysis. We have recently demonstrated the potential use of some of the BMPs in promoting biomechanical features of healing tendons/ligaments. We also demonstrated that Sox9, a master regulator of chondrogenesis, may be used in gene therapy to treat intervertebral disc degeneration and articular cartilage injuries. These lines of investigation reflect our commitment to the true spirit of translational research in bone and musculoskeletal disorders.

One or more keywords matched the following items that are connected to He, Tong-Chuan

Item TypeName
Concept Stem Cells
Concept Tumor Stem Cell Assay
Concept Stem Cell Transplantation
Concept Embryonic Stem Cells
Concept Mesenchymal Stem Cell Transplantation
Concept Multipotent Stem Cells
Concept Pluripotent Stem Cells
Concept Neoplastic Stem Cells
Academic Article Inhibitor of DNA binding/differentiation helix-loop-helix proteins mediate bone morphogenetic protein-induced osteoblast differentiation of mesenchymal stem cells.
Academic Article Transcriptional characterization of bone morphogenetic proteins (BMPs)-mediated osteogenic signaling.
Academic Article Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells.
Academic Article Regulation of osteogenic differentiation during skeletal development.
Academic Article BMP-9-induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/beta-catenin signalling.
Academic Article Wnt antagonist SFRP3 inhibits the differentiation of mouse hepatic progenitor cells.
Academic Article Hey1 basic helix-loop-helix protein plays an important role in mediating BMP9-induced osteogenic differentiation of mesenchymal progenitor cells.
Academic Article Neurogenesis-related genes expression profiling of mouse fibroblastic stem cells induced by Wnt signaling.
Academic Article Retinoic acid signalling induces the differentiation of mouse fetal liver-derived hepatic progenitor cells.
Academic Article Synergistic antitumor effect of the activated PPARgamma and retinoid receptors on human osteosarcoma.
Academic Article Retinoic acids potentiate BMP9-induced osteogenic differentiation of mesenchymal progenitor cells.
Academic Article Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells.
Academic Article Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation.
Academic Article Pre-activation of retinoid signaling facilitates neuronal differentiation of mesenchymal stem cells.
Academic Article Low serum concentration facilitates the differentiation of hepatic progenitor cells.
Academic Article The therapeutic potential of the Wnt signaling pathway in bone disorders.
Academic Article LIGHT delivery to tumors by mesenchymal stem cells mobilizes an effective antitumor immune response.
Academic Article The CCN proteins: important signaling mediators in stem cell differentiation and tumorigenesis.
Academic Article TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells.
Academic Article CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
Academic Article Epigenetic regulation of mesenchymal stem cells: a focus on osteogenic and adipogenic differentiation.
Academic Article Biphasic effects of TGFß1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells.
Academic Article Mesenchymal Progenitor Cells and Their Orthopedic Applications: Forging a Path towards Clinical Trials.
Academic Article BMP-9 induced osteogenic differentiation of mesenchymal stem cells: molecular mechanism and therapeutic potential.
Academic Article Mesenchymal stem cells: Molecular characteristics and clinical applications.
Academic Article Osteosarcoma development and stem cell differentiation.
Academic Article A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells.
Academic Article Conditional immortalization establishes a repertoire of mouse melanocyte progenitors with distinct melanogenic differentiation potential.
Academic Article Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs).
Academic Article Conditionally immortalized mouse embryonic fibroblasts retain proliferative activity without compromising multipotent differentiation potential.
Academic Article Bone morphogenetic proteins in craniofacial surgery: current techniques, clinical experiences, and the future of personalized stem cell therapy.
Academic Article BMP9 signaling in stem cell differentiation and osteogenesis.
Academic Article Distinct osteogenic activity of BMPs and their orthopaedic applications.
Academic Article BMP9-regulated angiogenic signaling plays an important role in the osteogenic differentiation of mesenchymal progenitor cells.
Academic Article Establishment and characterization of the reversibly immortalized mouse fetal heart progenitors.
Academic Article The piggyBac transposon-mediated expression of SV40 T antigen efficiently immortalizes mouse embryonic fibroblasts (MEFs).
Academic Article Reversibly Immortalized Mouse Articular Chondrocytes Acquire Long-Term Proliferative Capability While Retaining Chondrogenic Phenotype.
Academic Article Crosstalk between Wnt/ß-catenin and estrogen receptor signaling synergistically promotes osteogenic differentiation of mesenchymal progenitor cells.
Academic Article Endoplasmic reticulum (ER) stress inducible factor cysteine-rich with EGF-like domains 2 (Creld2) is an important mediator of BMP9-regulated osteogenic differentiation of mesenchymal stem cells.
Academic Article Cross-talk between EGF and BMP9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells.
Academic Article Characterization of scaffold carriers for BMP9-transduced osteoblastic progenitor cells in bone regeneration.
Academic Article Characterization of constitutive promoters for piggyBac transposon-mediated stable transgene expression in mesenchymal stem cells (MSCs).
Academic Article Noggin resistance contributes to the potent osteogenic capability of BMP9 in mesenchymal stem cells.
Academic Article Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology.
Academic Article Functional characteristics of reversibly immortalized hepatic progenitor cells derived from mouse embryonic liver.
Academic Article Comparison of proliferation and differentiation potential between mouse primary hepatocytes and embryonic hepatic progenitor cells in vitro.
Academic Article BMP9 regulates cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells.
Academic Article A simplified and versatile system for the simultaneous expression of multiple siRNAs in mammalian cells using Gibson DNA Assembly.
Academic Article Decellularized liver scaffolds effectively support the proliferation and differentiation of mouse fetal hepatic progenitors.
Academic Article Canonical Wnt signaling acts synergistically on BMP9-induced osteo/odontoblastic differentiation of stem cells of dental apical papilla (SCAPs).
Academic Article Inhibition of histone deacetylases potentiates BMP9-induced osteogenic signaling in mouse mesenchymal stem cells.
Academic Article Hedgehog signaling is involved in the BMP9-induced osteogenic differentiation of mesenchymal stem cells.
Academic Article Overexpression of Ad5 precursor terminal protein accelerates recombinant adenovirus packaging and amplification in HEK-293 packaging cells.
Academic Article Bone morphogenetic protein-9 effectively induces osteo/odontoblastic differentiation of the reversibly immortalized stem cells of dental apical papilla.
Academic Article Adenovirus-mediated gene transfer in mesenchymal stem cells can be significantly enhanced by the cationic polymer polybrene.
Academic Article 5-azacytidine promotes terminal differentiation of hepatic progenitor cells.
Academic Article Characterization of Reversibly Immortalized Calvarial Mesenchymal Progenitor Cells.
Academic Article TqPCR: A Touchdown qPCR Assay with Significantly Improved Detection Sensitivity and Amplification Efficiency of SYBR Green qPCR.
Academic Article Three-dimensional co-culture of hepatic progenitor cells and mesenchymal stem cells in vitro and in vivo.
Academic Article Activation of PKA/CREB Signaling is Involved in BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells.
Academic Article The Prodomain-Containing BMP9 Produced from a Stable Line Effectively Regulates the Differentiation of Mesenchymal Stem Cells.
Academic Article The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies.
Academic Article [Effects of Plasmid Fibroblast Growth Factor-2 Magnetic Chitosan Gelatin Microspheres on Proliferation and Differentiation of Mesenchymal Stem Cells].
Academic Article A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells.
Academic Article Nanoparticulate Mineralized Collagen Scaffolds and BMP-9 Induce a Long-Term Bone Cartilage Construct in Human Mesenchymal Stem Cells.
Academic Article Bone morphogenetic protein 9 (BMP9) induces effective bone formation from reversibly immortalized multipotent adipose-derived (iMAD) mesenchymal stem cells.
Academic Article For your eyes only: Harnessing human embryonic stem cell-derived retinal pigment epithelial cells to improve impaired vision.
Academic Article BMP signaling in mesenchymal stem cell differentiation and bone formation.
Academic Article Wnt/ß-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance.
Academic Article Repair of critical sized cranial defects with BMP9-transduced calvarial cells delivered in a thermoresponsive scaffold.
Academic Article NEL-Like Molecule-1 (Nell1) Is Regulated by Bone Morphogenetic Protein 9 (BMP9) and Potentiates BMP9-Induced Osteogenic Differentiation at the Expense of Adipogenesis in Mesenchymal Stem Cells.
Academic Article Notch Signaling Augments BMP9-Induced Bone Formation by Promoting the Osteogenesis-Angiogenesis Coupling Process in Mesenchymal Stem Cells (MSCs).
Academic Article Noncanonical Wnt signaling plays an important role in modulating canonical Wnt-regulated stemness, proliferation and terminal differentiation of hepatic progenitors.
Academic Article Gelatin-Derived Graphene-Silicate Hybrid Materials Are Biocompatible and Synergistically Promote BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells.
Academic Article Wnt and BMP Signaling Crosstalk in Regulating Dental Stem Cells: Implications in Dental Tissue Engineering.
Academic Article Engineering the Rapid Adenovirus Production and Amplification (RAPA) Cell Line to Expedite the Generation of Recombinant Adenoviruses.
Academic Article CRISPR/Cas9-Mediated Genome Editing Corrects Dystrophin Mutation in Skeletal Muscle Stem Cells in a Mouse Model of Muscle Dystrophy.
Academic Article lncRNA H19 mediates BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) through Notch signaling.
Academic Article Signal transduction in the erythropoietin receptor system.
Academic Article [Regulatory effect of faciogenital dysplasia 6 gene on hepatic stem cell differentiation].
Academic Article The beta-catenin binding domain of adenomatous polyposis coli is sufficient for tumor suppression.
Academic Article Neural EGF-like protein 1 (NELL-1): Signaling crosstalk in mesenchymal stem cells and applications in regenerative medicine.
Academic Article Induced maturation of hepatic progenitor cells in vitro.
Academic Article lncRNA H19 mediates BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) through Notch signaling.
Academic Article BMP9 induces osteogenesis and adipogenesis in the immortalized human cranial suture progenitors from the patent sutures of craniosynostosis patients.
Academic Article BMP9-induced osteoblastic differentiation requires functional Notch signaling in mesenchymal stem cells.
Academic Article Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis.
Academic Article A thermoresponsive, citrate-based macromolecule for bone regenerative engineering.
Academic Article Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells (MSCs).
Academic Article Reversibly immortalized hepatic progenitor cell line containing double suicide genes.
Academic Article Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference.
Academic Article Periodic acid-Schiff staining method for function detection of liver cells is affected by 2% horse serum in induction medium.
Academic Article CRISPR/Cas9-mediated reversibly immortalized mouse bone marrow stromal stem cells (BMSCs) retain multipotent features of mesenchymal stem cells (MSCs).
Academic Article Reversibly immortalized human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are responsive to BMP9-induced osteogenic and adipogenic differentiation.
Academic Article Effects of Brain-Derived Neurotrophic Factor on MicroRNA Expression Profile in Human Endothelial Progenitor Cells.
Academic Article A pH-Triggered, Self-Assembled, and Bioprintable Hybrid Hydrogel Scaffold for Mesenchymal Stem Cell Based Bone Tissue Engineering.
Academic Article Thermoresponsive Citrate-Based Graphene Oxide Scaffold Enhances Bone Regeneration from BMP9-Stimulated Adipose-Derived Mesenchymal Stem Cells.
Academic Article Dentinogenesis and Tooth-Alveolar Bone Complex Defects in BMP9/GDF2 Knockout Mice.

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