Family with sequence similarity 20 member B regulates osteogenic differentiation of bone marrow mesenchymal stem cells on titanium surfaces
Source abstract
Abstract
Successful bone regeneration on titanium (Ti) surfaces is a key process in dental implant treatment. Bone marrow mesenchymal stem cells (BMSCs) are fundamental cellular components of this process, and their early recruitment, proliferation, and differentiation into bone-forming osteoblasts are crucial. A proteoglycan (PG)-rich layer has been reported to exist between Ti surfaces and bones; however, the molecules that could potentially affect the formation of this layer remain unknown. Family with sequence similarity 20 member B (FAM20B) is a newly identified kinase that regulates the synthesis of glycosaminoglycans, an important component of the PG-rich layer. Because FAM20B is also closely associated with bone development, in this study, we examined the function of FAM20B in osteogenic differentiation of BMSCs on Ti surfaces. For this, BMSC cell lines with knocked down FAM20B (shBMSCs) were cultured on Ti surfaces. The results showed that the depletion of FAM20B reduced the formation of a PG-rich layer between the Ti surfaces and cells. The shBMSCs exhibited downregulated expression of osteogenic marker genes (ALP and OCN) and decreased mineral deposition. Moreover, shBMSCs reduced the molecular levels of p-ERK1/2, which plays an important role in MSC osteogenesis. The nuclear translocation of RUNX2, an important transcription factor for osteogenic differentiation, on the Ti surfaces is inhibited by the depletion of FAM20B in BMSCs. Moreover, the depletion of FAM20B reduced the transcriptional activity of RUNX2, which is important in regulating the expression of osteogenic genes. STATEMENT OF SIGNIFICANCE: Bone healing and regeneration on implanted titanium surfaces is a cell-material interaction. Such an interaction is enabled by bone marrow mesenchymal stem cells (BMSCs), and their early recruitment, proliferation, and differentiation into bone-forming osteoblasts are essential for bone healing and osseointegration. In this study, we found that the family with sequence similarity 20-B influenced the formation of a proteoglycan rich layer between BMSCs and the titanium surface and regulated the differentiation of BMSCs into bone-forming osteoblasts. We believe that our study contributes significantly to the further exploration of bone healing and osseointegration mechanisms on implanted titanium surfaces.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Proteoglycans and glycosaminoglycans research · Osteoarthritis Treatment and Mechanisms · Periodontal Regeneration and Treatments
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (43)
Show source-provided references
1. Exosomes influence the behavior of human mesenchymal stem cells on titanium surfaces10.1016/j.biomaterials.2019.119571 ↗
2. In situ construction of a nano-structured akermanite coating for promoting bone formation and osseointegration of Ti-6Al-4V implants in a rabbit osteoporosis model10.1039/D1TB01917A ↗
3. Macrophage response to hydrophilic biomaterials regulates MSC recruitment and T-helper cell populations10.1016/j.biomaterials.2018.08.029 ↗
4. Electron microscopic analysis of the bone-titanium interface10.3109/17453678308992868 ↗
5. Glycosaminoglycan degradation reduces mineralized tissue-titanium interfacial strength10.1002/jbm.a.30624 ↗
6. Synthesis and sorting of proteoglycans10.1242/jcs.113.2.193 ↗
7. Heparan sulfate proteoglycans10.1101/cshperspect.a004952 ↗
8. Chondroitin-4-sulfate transferase-1 depletion inhibits formation of a proteoglycan-rich layer and alters immunotolerance of bone marrow mesenchymal stem cells on titanium oxide surfaces10.1016/j.actbio.2020.07.034 ↗
9. Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis10.1073/pnas.1417993111 ↗
10. Inactivation of Fam20b in the neural crest-derived mesenchyme of mouse causes multiple craniofacial defects10.1111/eos.12563 ↗
11. Inactivation of Fam20B in joint cartilage leads to chondrosarcoma and postnatal ossification defects10.1038/srep29814 ↗
12. XYLT1 mutations in Desbuquois dysplasia type 210.1016/j.ajhg.2014.01.020 ↗
13. A novel gene (FAM20B encoding glycosaminoglycan xylosylkinase) for neonatal short limb dysplasia resembling Desbuquois dysplasia10.1111/cge.13530 ↗
14. Stimulatory effects of basic fibroblast growth factor and bone morphogenetic protein-2 on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells10.1359/jbmr.1997.12.10.1606 ↗
15. Differentiation of human marrow stromal precursor cells: bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation10.1359/jbmr.1999.14.9.1522 ↗
16. Expression profiling and functional analysis of WNT signaling mechanisms in mesenchymal stem cells10.1634/stemcells.22-5-849 ↗
17. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression10.1074/jbc.M500608200 ↗
18. Bone morphogenetic protein regulation of early osteoblast genes in human marrow stromal cells is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling10.1210/en.2005-0303 ↗
19. Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1/2 and protein kinase C signaling10.1074/jbc.M805432200 ↗
20. Overexpression of Dlx2 enhances osteogenic differentiation of BMSCs and MC3T3-E1 cells via direct upregulation of Osteocalcin and Alp10.1038/s41368-019-0046-1 ↗
21. Role of Cbfa1 in osteoblast differentiation and function
22. Erk pathway and activator protein 1 play crucial roles in FGF2-stimulated premature cranial suture closure10.1002/dvdy.10319 ↗
23. Inactivation of FAM20B causes cell fate changes in annulus fibrosus of mouse intervertebral disc and disc defects via the alterations of TGF-beta and MAPK signaling pathways10.1016/j.bbadis.2019.165555 ↗
24. Inactivation of Fam20B in the dental epithelium of mice leads to supernumerary incisors10.1111/eos.12222 ↗
25. Runx2, a multifunctional transcription factor in skeletal development10.1002/jcb.10276 ↗
26. Regulation of skeletal development by the Runx family of transcription factors10.1002/jcb.20420 ↗
27. Building strong bones: molecular regulation of the osteoblast lineage10.1038/nrm3254 ↗
28. Runx2: Structure, function, and phosphorylation in osteoblast differentiation10.1016/j.ijbiomac.2015.04.008 ↗
29. Postnatal Runx2 deletion leads to low bone mass and adipocyte accumulation in mice bone tissues10.1016/j.bbrc.2019.07.014 ↗
30. Klinger · J E Lemons Crit. Rev. Oral Biol. Med. · 1998 · 9 · 44910.1177/10454411980090040401 ↗
31. The effects of syndecan on osteoblastic cell adhesion onto nano-zirconia surface10.2147/IJN.S263053 ↗
32. Matrix protein biglycan induces osteoblast differentiation through extracellular signal-regulated kinase and smad pathways10.1248/bpb.33.1891 ↗
33. Activating and inhibitory heparin sequences for FGF-2 (basic FGF). Distinct requirements for FGF-1, FGF-2, and FGF-410.1016/S0021-9258(20)80471-2 ↗
34. Proteoglycans and glycosaminoglycans in stem cell homeostasis and bone tissue regeneration10.3389/fcell.2021.760532 ↗
35. Synergism between Wnt3a and heparin enhances osteogenesis via a phosphoinositide 3-kinase/Akt/RUNX2 pathway10.1074/jbc.M110.122069 ↗
36. Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation10.1101/gad.1119303 ↗
37. Endothelial production of MCP-1: modulation by heparin and consequences for mononuclear cell activation10.1046/j.1365-2567.1997.00385.x ↗
38. Fibroblast growth factor 2 induction of the osteocalcin gene requires MAPK activity and phosphorylation of the osteoblast transcription factor, Cbfa1/Runx210.1074/jbc.M206057200 ↗
39. Identification and functional characterization of ERK/MAPK phosphorylation sites in the Runx2 transcription factor10.1074/jbc.M109.040980 ↗
40. FGF2-activated ERK mitogen-activated protein kinase enhances Runx2 acetylation and stabilization10.1074/jbc.M109.055053 ↗
41. Exosome: a novel approach to stimulate bone regeneration through regulation of osteogenesis and angiogenesis10.3390/ijms17050712 ↗
42. Heparan sulfate in angiogenesis: a target for therapy
43. Angiogenesis and intramembranous osteogenesis10.1002/dvdy.23992 ↗