An insight of Osthole, Bone marrow mesenchymal stem cells, and BMP-9 loaded carbon-based scaffolds as a Biomaterial candidate in Osteoporosis Therapy: A Narrative Review

Background: More than 200 million people worldwide diagnosed with osteoporosis, a degenerative condition characterized by decreasing bone mineral density. Although oral bisphosphonates are the most used form of treatment for osteoporosis, they have the potential to result in osteonecrosis. Osthole bone marrow mesenchymal stem cells (OBMMSCs) are combination of bone marrow mesenchymal stem cells (BMMSCs) and coumarin derivatives from Cnidium monnieri act as anti-inflammatory and anti-osteoporosis agents. The use of OBMMSCs in triad tissue engineering necessitates using a growth factor and a scaffold, which are combined with BMP-9 incorporated in carbon-based scaffold namely nano hydroxyapatite/collagen I/multi-walled carbon nanotubes (nHA/ColI/MWCNTs) scaffold to promote better loading. The combination of OBMMSCs and BMP-9 loaded nHA/ColI/MWCNTs scaffold has potential to increase OBMMSC differentiation into osteoblasts, resulting in increased bone remodeling and a better outcome in osteoporosis therapy. Purpose: To analyze the potential of OBMMSCs and BMP-9 loaded nHA/ColI/MWCNTs scaffolds as osteoporosis therapy. Discussion: Osthole enhances BMMSCs differentiation via activation of cAMP/CERK and Wnt/β-catenin/BMP signaling pathways. Osthole increases alkaline phosphatase (ALP) expression that stimulates osteogenesis. Meanwhile, in the Wnt/β-catenin-BMP pathway, osthole initiates Wnt binding to the Fz receptor so that β-catenin expression increases. β-catenin, together with Runx2, reduces the expression of GSK-3β, thereby increasing BMMSCs differentiation into osteoblasts. BMP-9 loaded nHA/COLI/MWCNTS scaffold promotes the differentiation of BMMSCs into osteoblasts by increasing the supply of collagen and calcium, as well as angiogenesis, which increases vascularity. Conclusion: OBMMSCs and BMP-9 loaded nHA/ColI/MWCNT scaffold have the potential to treat osteoporosis.