Abstract
Bone substitute materials loaded with mediators that stimulate fracture healing are demanded in the clinical treatment in trauma surgery and orthopedics. Brain-derived neurotrophic factor (BDNF) enhances the proliferation and differentiation of mesenchymal stem cells into osteoblast. To load the implants with BDNF, a drug delivery system that allows the release of BDNF under spatiotemporal control would improve functionality. Polyelectrolyte complex nanoparticles (PECNP) have been reported as a suitable drug delivery system. The suitability of PECNP in contact with osteocytes as the main cell type of bone is not known so far. Thus, we aimed to verify that BDNF and PECNP loaded with BDNF (PECNP+BDNF) as well as pure PECNP have no negative effects on osteocytes in vitro. Therefore, the murine osteocyte cell line MLO-Y4 was treated with BDNF and PECNP+BDNF. The effects on proliferation were analyzed by the BrdU test (n = 5). The results demonstrated a significant increase in proliferation 24 h after BDNF application, whereas PECNP+BDNF did not lead to significant changes. Thus, we conclude that BDNF is an appropriate mediator to stimulate osteocytes. Since the addition of PECNP did not affect the viability of osteocytes, we conclude that PECNP are a suitable drug delivery system for bone implants.
Highlights
The most abundant cells in the skeleton are osteocytes embedded in bone matrix
Since it was not possible to increase the concentration of Brain-derived neurotrophic factor (BDNF) that was loaded to Polyelectrolyte complex nanoparticles (PECNP), it was decided to increase the amount of PECNP added to the cell cultures
We conclude that BDNF stimulated the proliferation of cells of the murine osteocyte cell line
Summary
The most abundant cells in the skeleton are osteocytes embedded in bone matrix. They are able to sense the mechanical load, orchestrate bone remodeling, and regulate bone formation [1].Osteocytes communicate with osteoblasts and osteoclasts via cell contacts through dendritic processes or soluble factors that are secreted into the pericellular space and distributed through the lacunocanalicular network [2]. The most abundant cells in the skeleton are osteocytes embedded in bone matrix. They are able to sense the mechanical load, orchestrate bone remodeling, and regulate bone formation [1]. Osteocytes communicate with osteoblasts and osteoclasts via cell contacts through dendritic processes or soluble factors that are secreted into the pericellular space and distributed through the lacunocanalicular network [2]. Mature osteocytes synthesize the protein sclerostin (gene name: SOST), which is an important negative regulator of bone formation by osteoblasts [1]. The decoy receptor osteoprotegerin (OPG) is able to block the binding site of RANKL and can inhibit the stimulation of osteoclasts by RANKL [3]. OPG is synthesized by osteocytes as well as by osteoblasts
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