Enamel Matrix Derivative has No Effect on the Chondrogenic Differentiation of Mesenchymal Stem Cells

Abstract

Background: Treatment of large bone defects due to trauma, tumor resection, or congenital abnormalities is challenging. Bone tissue engineering using mesenchymal stem cells (MSCs) represents a promising treatment option. However, the quantity and quality of engineered bone tissue are not sufficient to fill large bone defects. The aim of this study was to determine if the addition of enamel matrix derivative (EMD) improves in vitro chondrogenic priming of MSCs to ultimately improve in vivo MSC mediated endochondral bone formation.Methods: MSCs were chondrogenically differentiated in 2.0 × 105 cell pellets in medium supplemented with TGFβ3 in the absence or presence of 1, 10, or 100 μg/mL EMD. Samples were analyzed for gene expression of RUNX2, Col II, Col X, and Sox9. Protein and glycoaminoglycan (GAG) production were also investigated via DMB assays, histology, and immunohistochemistry. Osteogenic and adipogenic differentiation capacity were also assessed.Results: The addition of EMD did not negatively affect chondrogenic differentiation of adult human MSCs. EMD did not appear to alter GAG production or expression of chondrogenic genes. Osteogenic and adipogenic differentiation were also unaffected though a trend toward decreased adipogenic gene expression was observed.Conclusion: EMD does not affect chondrogenic differentiation of adult human MSCs. As such the use of EMD in combination with chondrogenically primed MSCs for periodontal bone tissue repair is unlikely to have negative effects on MSC differentiation.

Modulation of immune-inflammatory responses through surface modifications of biomaterials to promote bone healing and regeneration

“…For instance, in the context of periodontal regeneration, only Emdogain and hyaluronic acid have been approved clinically, however, it still needs improvement to ensure predictability of tissue regeneration. 130,131 Biological scaffolds show degradation upon long term storage. Furthermore, depending on the source, they exhibit high variability in terms of reproducibility and compatibility.…”

Human Trials on the Prevention of Tunnel Widening by the Emdogain in Anterior Cruciate Ligament Reconstruction

“…EMD is widely used in periodontal treatments to promote bone formation in the clinical setting [25]. EMD has the ability to stimulate cell proliferation and mineralization of both preosteoblasts and osteoblasts and induce the differentiation of MSCs into osteoblasts and chondrocytes [9][10][11][12]. Because of these characteristics and safety in clinical use, Kadonishi et al examined the efficacy of EMD administration on tendon-bone healing of the tunnel in ACLR in a rat model.…”

“…Emdogain (EMD) is made from the enamel matrix proteins of minor porcine teeth and is used as an osteopromotive agent for bone augmentation and regeneration [8]. EMDs stimulate the cellular proliferation and mineralization of osteoblasts and promote the differentiation of osteoblasts and chondrocytes from mesenchymal stem cells [9][10][11][12]. With the expectation of osteogenesis in the tendon-bone junction by EMD in ACLR, an animal study using rats revealed the feasibility of EMD in preventing tunnel widening [13].…”

Enamel matrix derivative (EMD) enhances the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs)

“…Although EMD is widely utilized in periodontal treatments and the new cementum is often observed [8], relevant report on alveolar bone formation remains scant [10,11]. On the other hand, EMD was also reported to stimulate cellular proliferation and the mineralization of both pre-osteoblasts and osteoblasts [12][13][14], resulting in an inhibition in the myogenic and lipogenic differentiation of pluripotent mesenchymal cells and leading to the induction of their differentiation into osteoblasts and chondrocytes [13,15].…”