Canine Oral Mucosal Fibroblasts Differentiate into Osteoblastic Cells in Response to BMP‐2

Abstract

Several lines of evidence show that transplantation of osteoblastic cells or genetically engineered nonosteogenic cells expressing osteoblastrelated genes into bone defects effectively promotes bone regeneration. To extend this possibility, we investigated whether oral mucosal fibroblasts are capable of differentiating into osteoblastic cells by conducting in vitro and in vivo experiments. We investigated the effects of bone morphogenetic protein-2 (BMP-2) on osteoblast differentiation of cultured fibroblasts isolated from canine buccal mucosa. We also transplanted green fluorescence protein (GFP)-expressing fibroblasts with gelatin/BMP-2 complexes into the subfascial regions of athymic mice, and investigated the localization of GFP-positive cells in the ectopically formed bones. The cultured canine buccal mucosal fibroblasts differentiated into osteoblastic cells by increasing their alkaline phosphatase (ALP) activity and Osteocalcin, Runx2, and Osterix mRNA expression levels in response to BMP-2. Transplantation experiments of GFP-expressing oral mucosal fibroblasts with gelatin/BMP-2 complexes revealed that 17.1% of the GFP-positive fibroblasts differentiated into ALP-positive cells, and these cells accounted for 6.2% of total ALP-positive cells in the ectopically formed bone. This study suggests that oral mucosal fibroblasts can differentiate into osteogenic cells in response to BMP-2. Thus, these cells are potential candidates for cell-mediated bone regeneration therapy in dentistry. Anat Rec, 295:1327Rec, 295: -1335

Sphere-Derived Multipotent Progenitor Cells Obtained From Human Oral Mucosa Are Enriched in Neural Crest Cells

“…We observed a hard tissue regeneration capacity even in the subcutaneous region. Umehara et al reported that canine oral mucosaderived fibroblasts could effectively differentiate into osteoblasts in response to BMP-2 [51]; thus, their findings support the results of our study. However, we did not observe tumor formation [4].…”

Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors

“…Various authors report that co-culture with osteoblasts [87] or treatment with BMP-2 or -7 [112,113] can induce fibroblasts to express typical osteoblast genes such as ALP and OCN, improving tendon-to-bone integration [113]. In addition, fibroblasts have also been reported to transdifferentiate into chondrocytes when transfected with Sox9 [114] or stimulated with cartilage-derived morphogenetic protein 1 (CDMP1) [115].…”

Bushen-Qiangdu-Zhilv decoction inhibits osteogenic differentiation of rat fibroblasts by regulating connexin 43

“…Cbfα1 is a key transcription factor and regulator of osteogenic differentiation, which may also regulate the expression of other osteogenic differentiation marker genes and osteogenic phenotype related genes such as alkaline phosphatase (ALP), OC, type I collagen, thereby enhancing the expression of osteogenic phenotypes to promote osteogenic differentiation and bone formation (23)(24)(25). Thus, the increased expression of Cbfα1 protein in fibroblasts is usually considered to be a sign of the osteogenic differentiation of fibroblasts, whereas the decreased expression of Cbfα1 may indicate the suppression of osteogenic differentiation (20).…”

“…Cbfα1 protein expression has been demonstrated to be markedly increased in fibroblasts compared to the fibroblasts without BMP-2 induction, which are differentiated into osteogenic cells in response to BMP-2 (20). Notably, it has been reported that the expression of Cbfα1 is regulated by the BMP signal pathway (26).…”

“…BMP-2 is considered to serve a crucial role in osteoblast differentiation and the subsequent bone formation by stimulating Cbfα1 (18), which is essential for osteoblast differentiation and bone formation (19). A previous reports demonstrated that fibroblasts could differentiate into osteogenic cells in response to BMP-2 at concentration of 200 µg/ml (20). Therefore, 200 µg/ml BMP-2 was utilized in the present study to construct in vitro model for new bone formation of AS patients.…”