Biglycan regulates bone development and regeneration
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ABSTRACT:
PROVIDER: PRJNA791910 | ENA |
REPOSITORIES: ENA
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Project description:Endochondral bone development and regeneration relies on activation and proliferation of periosteum derived-cells (PDCs). Biglycan (Bgn), a small proteoglycan found in extracellular matrix , is known to be expressed in bone and cartilage, however little is known about its influence during bone development. Here we link Bgn with osteoblast maturation starting during embryonic development that with aging affects bone integrity and strength. Bgn gene deletion reduced the inflammatory response after fracture, leading to impaired periostal expansion and callus formation. Using novel 3D scaffold and analyzing newborn bones, we found that Bgn is required for the cartilage-bone transition of PDCs during endochondral bone development. The absence of Bgn led to accelerated bone development with high levels of osteopontin which appeared to be detrimental to the structural integrity of the bone. Collectively, our study identifies Bgn as an important factor in PDCs activation during bone development and bone regeneration after fracture.
2023-03-01 | GSE192542 | GEO
Project description:Development of MDM2-targeting PROTAC technology for advancing bone regeneration
| PRJNA1074395 | ENA
Project description:Loss or damage to the mandible due to trauma, treatment of oral malignancies, and other diseases is currently treated using bone grafting techniques that suffer from numerous shortcomings and contraindications. Zebrafish naturally heal large injuries to their mandibular bone, and thus offer an opportunity to understand how to boost intrinsic healing ability. Using a novel her6:mCherry Notch reporter, we show that canonical Notch signaling is induced during the initial stages of cartilage callus formation in both mesenchymal cells and chondrocytes. We also show that modulation of Notch signaling during the initial postoperative period results in lasting changes to regenerate bone quantity one month later. Notch signaling is required for mandibular bone healing, as pharmacological inhibition of Notch signaling blocks cartilage callus formation and results in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates regenerative ossification. Mechanistically, we report that postoperative Notch signaling regulates multiple phases of chondroid regeneration and patterns callus metabolic landscape. Given conserved functions of Notch signaling in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing may have therapeutic value.
2022-03-07 | PXD027280 | Pride
Project description:The project investigated chirality-biased proteome during the early stage of bone regeneration on day 3 and day 7.
2023-07-12 | PXD043696 |
Project description:Endochondral bone development and regeneration relies on activation and proliferation of periosteum derived-cells (PDCs). Biglycan (Bgn), a small proteoglycan found in extracellular matrix, is known to be expressed in bone and cartilage, however little is known about its influence during bone development. Here we link biglycan with osteoblast maturation starting during embryonic development that later affects bone integrity and strength. Biglycan gene deletion reduced the inflammatory response after fracture, leading to impaired periosteal expansion and callus formation. Using a novel 3D scaffold with PDCs, we found that biglycan could be important for the cartilage phase preceding bone formation. The absence of biglycan led to accelerated bone development with high levels of osteopontin, which appeared to be detrimental to the structural integrity of the bone. Collectively, our study identifies biglycan as an influencing factor in PDCs activation during bone development and bone regeneration after fracture.
| S-EPMC9979216 | biostudies-literature
Project description:Endochondral ossification (EO) is the natural route for the regeneration of large and mechanically challenged bone defects. Regeneration occurs via a fibrocartilagenous phase which turns into bone upon vascularization and the formation of a transient collagen type X extra cellular matrix. These two critical initiator of EO are mediated by Hedgehog proteins. We investigated a tissue engineering approach using Sonic Hedgehog (Shh) as a pleiotropic factor regulating the in vitro formation of a vascularized bone tissue precursor for in vivo endochondral bone formation. The tissue engineered graft was formed using human mesenchymal stem cells and prevascularized using human umbilical vein endothelial cells. We show that Shh induced, in vitro, the maturation of the engineered vascular network along with the expression of collagen type X which resulted, in vivo, in an improved vascularization and the rapid formation of large amounts of osteoids through EO. Osteoids further matured into, currently unmatched, clinically relevant amount of lamellar bone including osteoclasts, bone lining cells and bone marrow-like cavities. This result suggests that Hh is a master regulator of EO allowing for the formation of complex tissues with considerable therapeutic potential for bone regeneration. The effect of Cyclopamine on expression of Hedgehog, angiogenesis and axon guidance marker genes was analyzed by seeding a coculture of 92% hMSCs and 8% huvEC supplemented or not in cyclopamine, for 12 days
2012-09-01 | E-GEOD-22293 | biostudies-arrayexpress
Project description:STAT3 regulates osteogenesis, making it critical for skeletal development and bone homeostasis
| PRJNA726815 | ENA
Project description:While cellular energy metabolism regulates tissue regeneration, it remains as a challenge with its limited understanding of activation by engineered scaffolds to regenerate tissue or organ for therapeutic purpose. This study presents a biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [abbreviated as P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), functioning as an endogenous bioenergetic molecule to facilitate bone regeneration and promote cellular anabolism via generations of adenosine triphosphate (ATP) and citrate that enhance the progression of human bone marrow mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our studies demonstrate that 3HB not only significantly enhances in vitro ATP generation to elevate mitochondrial membrane potential (ΔΨm) and capillary-like tube formation, but also increases the content of intermediate metabolite, namely, citrate, in tricarboxylic acid (TCA) cycle, and ultimately promotes the formation of citrate-containing apatite during osteogenesis of hBMSCs. Furthermore, 3HB administration increases the bone mass in rats with ovariectomy (OVX)-induced osteoporosis. Results also show that the P(3HB-co-4HB) scaffold significantly enhances long-term induced bone repair in a rat model with critical-sized calvarial defects, compared to the commercialized available poly-L-lactic acid (PLLA) scaffold. Collectively, these findings uncover a previously undefined role of 3HB in promoting osteogenic differentiation of hBMSCs and highlight that the P(3HB-co-4HB) scaffold functions as a metabolically activated energetic material for bone regeneration.
2023-09-03 | GSE242022 | GEO
Project description:Bone fracture healing requires skeletal stem cells (SSCs), which facilitate intramembranous ossification and endochondral ossification in long bone fractures. Although the periosteum is necessary for bone homeostasis and regeneration, the in vivo origin and regulatory mechanisms of periosteal SSCs (P-SSCs) remain unclear. Here, we identified Postn+ P-SSCs at the cambium layer of the periosteum that actively orchestrate regeneration in response to bone injury. Notably, the Postn+ P-SSCs that arise during bicortical fractures are likely derived from Gli1+ P-SSCs. In addition, Postn+ cell ablation compromises cortical bone homeostasis and bone regeneration. The IGF signal is indispensable in the regulatory effect of Postn+ P-SSCs on bicortical fractures since the genetic deletion of Igf1r in Postn+ cells dampens bone fracture healing. Taken together, adult Postn+ cells are region-specific P-SSCs that contribute to bone homeostasis and regeneration and are partially dependent upon IGF signaling.
2024-10-16 | GSE255137 | GEO
Project description:Endochondral ossification (EO) is the natural route for the regeneration of large and mechanically challenged bone defects. Regeneration occurs via a fibrocartilagenous phase which turns into bone upon vascularization and the formation of a transient collagen type X extra cellular matrix. These two critical initiator of EO are mediated by Hedgehog proteins. We investigated a tissue engineering approach using Sonic Hedgehog (Shh) as a pleiotropic factor regulating the in vitro formation of a vascularized bone tissue precursor for in vivo endochondral bone formation. The tissue engineered graft was formed using human mesenchymal stem cells and prevascularized using human umbilical vein endothelial cells. We show that Shh induced, in vitro, the maturation of the engineered vascular network along with the expression of collagen type X which resulted, in vivo, in an improved vascularization and the rapid formation of large amounts of osteoids through EO. Osteoids further matured into, currently unmatched, clinically relevant amount of lamellar bone including osteoclasts, bone lining cells and bone marrow-like cavities. This result suggests that Hh is a master regulator of EO allowing for the formation of complex tissues with considerable therapeutic potential for bone regeneration.
2012-09-01 | GSE22293 | GEO