Grafting bone defects or atrophic non-unions with mesenchymal stromal cells (MSCs)-based grafts is not yet successful. MSC-based grafts typically use undifferentiated or osteogenically differentiated MSCs and regenerate bone through intramembranous ossification. Endochondral ossification might be more potent but requires chondrogenic differentiation of MSCs. Here, we determined if chondrogenica...

Abstract Endochondral bone formation is fundamental for skeletal development. During this process, chondrocytes undergo multiple steps of differentiation and coordinated transition from a proliferating to hypertrophic stage, which critical advance Here, we identified the transcription factor Dmrt2 (double-sex mab-3 related 2) as Sox9-inducible gene that promotes chondrocyte hypertrophy in pre-h...

Healing As Revealed by In Vivo Imaging and Micro-CT analysis Li, X; Moore, D, Zhou FH; Robbins A; +Chen,Q +Brown University/Rhode Island Hospital, Providence, RI Jilin University, Changchun, Jilin Province, China [email protected],[email protected] INTRODUCTION: Matrilin-1(MATN1) is a cartilage specific, non-collagenous extracellular matrix protein produced by pre-hypertrophic chondrocytes in ...

Endochondral ossification is a major mode of bone that occurs as chondrocytes undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. We have identified a role for fibroblast growth factor receptor 3 (FGFR-3) in this process by disrupting the murine Fgfr-3 gene to produce severe and progressive bone dysplasia with enhanced and prolonged endochondral bone growth. This growt...

Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossificatio...

Engineered bone tissue is thought to be the ideal alternative for bone grafts in the treatment of related bone diseases. BMP9 has been demonstrated as one of the most osteogenic factors, and enhancement of BMP9-induced osteogenesis will greatly accelerate the development of bone tissue engineering. Here, we investigated the effect of insulin-like growth factor 1 (IGF1) on BMP9-induced osteogeni...

Background We had revealed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth by using transgenic and knockout mice: transgenic mice with targeted overexpression of CNP in cartilage develop prominent skeletal overgrowth [1], whereas mice depleted with CNP exhibit impaired endochondral bone growth [2]. We planned to translate this effect of CNP into the ther...

The parathyroid hormone-related peptide (PTHrP) gene was disrupted in murine embryonic stem cells by homologous recombination, and the null allele was introduced into the mouse germ line. Mice homozygous for the PTHrP null mutation died postnatally, probably from asphyxia, and exhibited widespread abnormalities of endochondral bone development. Histological examination revealed a diminution of ...

Limitations associated with demineralised bone matrix and other grafting materials have motivated the development of alternative strategies to enhance the repair of large bone defects. The growth plate (GP) of developing limbs contain a plethora of growth factors and matrix cues which contribute to long bone growth, suggesting that biomaterials derived from its extracellular matrix (ECM) may be...

BACKGROUND Endothelial cells (ECs) embedded in 3D matrices [matrix-embedded endothelial cells (MEECs)] of denatured collagen implanted around vascular access anastomoses preserve luminal patency. MEEC implant efficacy depends on embedded EC health. As the uremic milieu inhibits proliferation and induces apoptosis of ECs, we examined whether uremia might impact MEECs. METHODS ECs grown on 2D g...