Effects of BDNF and PEC Nanoparticles on Osteocytes

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.

Role of Extracellular Vesicles from Adipose Tissue- and Bone Marrow-Mesenchymal Stromal Cells in Endothelial Proliferation and Chondrogenesis

“… 49 BDNF is a growth factor described to play a role in the modulation of bone repair increasing the expression of the osteogenic markers. 50 IFN‐γ and IL‐1α are two important immunomodulators that trigger MSCs towards an anti‐inflammatory and pro‐trophic phenotype. 51 , 52 , 53 KLK3 is an angiogenesis suppressor.…”

Brain-Derived Neurotrophic Factor (BDNF) Enhances Osteogenesis and May Improve Bone Microarchitecture in an Ovariectomized Rat Model

“…During the osteoblast differentiation and mineralization of bone marrow-derived stromal cells, these cells drive a program of gene expression governed by various transcription factors [ 33 ]. Runx2 is regarded as the master transcription factor that promotes the differentiation of mesenchymal progenitors into osteoblasts by regulating the expression of osteogenesis-related genes at the early stage of osteoblastic differentiation, such as ALP, collagen alpha 1 type I, and osteocalcin [ 31 , 34 ].…”

Novel insights into osteocyte and inter-organ/tissue crosstalk

“…Limited by the difficulty of OCY extraction and culture technology, plenty of investigations showed that nearly all neurohormones had an effect on osteoblasts or osteoclasts (but not OCY) and exhibited bone anabolic or catabolic roles to regulate skeletal integrity; thus, the central control of OCY activity is almost blank ( 59 – 62 ). A recent study showed that the brain-derived neurotrophic factor, a growth factor mostly originated from the nervous system, plays a positive role on the proliferation of the murine osteocytic cell line MLO-Y4 ( 63 ). Co-injection of OCY into the brain exhibited tumor-suppressing capability through Lrp5, IL1ra, and β-catenin upregulation in brain metastases that occur from advanced breast cancer ( 25 ).…”