A5103171015- Bone health and osteoporosis research
- Bone Metabolism and Diseases
- Bone health and treatments
- Estrogen and related hormone effects
- Bone and Joint Diseases
- Wnt/β-catenin signaling in development and cancer
- Bone fractures and treatments
- Orthopaedic implants and arthroplasty
- Connective tissue disorders research
- Growth Hormone and Insulin-like Growth Factors
- Fibroblast Growth Factor Research
- Adenosine and Purinergic Signaling
- Inflammatory mediators and NSAID effects
- Anesthesia and Neurotoxicity Research
- Parathyroid Disorders and Treatments
- Spinal Cord Injury Research
- Cerebral Palsy and Movement Disorders
- Mitochondrial Function and Pathology
- Osteoarthritis Treatment and Mechanisms
- TGF-β signaling in diseases
- Alkaline Phosphatase Research Studies
- Tendon Structure and Treatment
- Endometriosis Research and Treatment
- Bone and Dental Protein Studies
- Cancer-related Molecular Pathways
Rutgers, The State University of New Jersey
2017-2024
China-Japan Friendship Hospital
2020-2024
Rutgers Cancer Institute of New Jersey
2022-2023
Amgen (United States)
2010-2023
Seventh People's Hospital of Shanghai
2021
UCB Pharma (United Kingdom)
2015-2021
Wuhou District People's Hospital, Chengdu
2021
Northwest Women's and Children's Hospital
2016-2019
Pfizer (United States)
1998-2010
Heze Municipal Hospital
2003
Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as key negative regulator of mass. We generated SOST knockout (KO) mice to gain more detailed understanding effects deficiency bone.Gene targeting was used inactivate and generate line KO mice. Radiography, densitometry, microCT, histomorphometry, mechanical testing were characterize impact male female Comparisons...
The development of bone-rebuilding anabolic agents for potential use in the treatment bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies humans and mice have shown that secreted protein sclerostin is key negative regulator formation, although magnitude extent sclerostin's role control formation aging skeleton still unclear. To study this unexplored area biology to assess pharmacologic effects inhibition, we used cell culture model identify neutralizing...
Abstract Therapeutic enhancement of fracture healing would help to prevent the occurrence orthopedic complications such as nonunion and revision surgery. Sclerostin is a negative regulator bone formation, treatment with sclerostin monoclonal antibody (Scl-Ab) results in increased formation mass animal models. Our objective was investigate effects systemic administration Scl-Ab two models healing. In both closed femoral model rats fibular osteotomy cynomolgus monkeys, significantly strength...
Abstract Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and preclinical animal models. Here we show increased levels Dickkopf-1 (DKK-1) animals treated antibody, suggesting a negative feedback mechanism that limits Wnt-driven formation. To test our hypothesis co-inhibition both factors further mass, engineer first-in-class bispecific antibody single residue pair mutations Fab region to promote efficient stable cognate light–heavy chain pairing....
Members of the transforming growth factor-β (TGF-β) superfamily and differentiation factors have been identified in a wide variety organisms, ranging from invertebrates to mammals. Bone morphogenetic proteins (BMPs) constitute subgroup belonging TGF-β superfamily. BMPs were initially by their ability induce endochondral bone formation at ectopic sites, suggesting critical role for this family development regeneration skeleton. They are also expressed nonskeletal sites during development,...
The P2X7 nucleotide receptor is an ATP-gated ion channel expressed widely in cells of hematopoietic origin. Our purpose was to explore the involvement bone development and remodeling by characterizing phenotype mice genetically modified disrupt [knockout (KO)]. Femoral length did not differ between KO wild-type (WT) littermates at 2 or 9 months age, indicating that does regulate longitudinal growth. However, displayed significant reduction total cortical content periosteal circumference...
The P2X7 nucleotide receptor (P2X7R) is an ATP-gated ion channel expressed in many cell types including osteoblasts and osteocytes. Mice with a null mutation of P2X7R have osteopenia load bearing bones, suggesting that the may be involved skeletal response to mechanical loading. We found sensitivity loading was reduced by up 73% (knock-out (KO)) mice. Release ATP primary calvarial occurred within 1 min onset fluid shear stress (FSS). After 30 FSS, P2X7R-mediated pore formation observed wild...
The purpose of this study was to evaluate the effects sclerostin inhibition by treatment with a antibody (Scl-AbII) on bone formation, mass, and strength in an aged, gonad-intact male rat model. Sixteen-month-old Sprague-Dawley rats were injected subcutaneously vehicle or Scl-AbII at 5 25 mg/kg twice per week for weeks (9-10/group). In vivo dual-energy X-ray absorptiometry (DXA) analysis showed that there marked increase areal mineral density lumbar vertebrae (L(1) L(5) ) long bones (femur...
ABSTRACT Bone formation can be remodeling-based (RBF) or modeling-based (MBF), the former coupled to bone resorption and latter occurring directly on quiescent surfaces. Unlike osteoanabolic therapies such as parathyroid hormone (PTH) 1-34 that increase remodeling thus both resorption, sclerostin antibody (Scl-Ab) increases while decreasing resorption. With this unique profile, we tested our hypothesis Scl-Ab primarily elicited MBF by examining bones from Scl-Ab–treated ovariectomized (OVX)...
Bone is accrued and maintained primarily through the coupled actions of bone-forming osteoblasts bone-resorbing osteoclasts. Cumulative in vitro studies indicated that proline-rich tyrosine kinase 2 (PYK2) a positive mediator osteoclast function activity. However, our investigation PYK2-/- mice did not reveal evidence supporting an essential for PYK2 osteoclasts either vivo or culture. We find have high bone mass resulting from unexpected increase formation. Consistent with findings, mouse...
Abstract Sclerostin is the product of SOST gene. Loss-of-function mutations in gene result a high-bone-mass phenotype, demonstrating that sclerostin negative regulator bone mass. Primarily expressed by osteocytes bone, reported to bind LRP5/6 receptor, thereby antagonizing canonical Wnt signaling and negatively regulating formation. We therefore investigated whether systemic administration sclerostin-neutralizing antibody would increase regeneration traumatized metaphyseal rats. Young male...
Abstract Sclerostin, a product of the SOST gene produced mainly by osteocytes, is potent negative regulator bone formation that appears to be responsive mechanical loading, with expression increasing following unloading. We tested ability murine sclerostin antibody (SclAbII) prevent loss in adult mice subjected hindlimb unloading (HLU) via tail suspension for 21 days. Mice (n = 11–17/group) were assigned control (CON, normal weight bearing) or HLU and injected either SclAbII (subcutaneously,...
Sclerostin antibody (Scl-Ab) increases osteoblast activity, in part through increasing modeling-based bone formation on previously quiescent surfaces. Histomorphometric studies have suggested that this might occur conversion of lining cells into active osteoblasts. However, direct data demonstrating Scl-Ab-induced osteoblasts are lacking. Here, we used vivo lineage tracing to determine if Scl-Ab promotes the periosteal and endocortical surfaces mice. Two independent, tamoxifen-inducible...
ABSTRACT The reconstruction of large osseous defects due to periodontitis is a challenge in regenerative therapy. Sclerostin, secreted by osteocytes, key physiological inhibitor osteogenesis. Pharmacologic inhibition sclerostin using sclerostin-neutralizing monoclonal antibody (Scl-Ab) thus increases bone formation, mass and strength models osteopenia fracture repair. This study assessed the therapeutic potential Scl-Ab stimulate alveolar regeneration following experimental (EP)....
Abstract Somatic hotspot mutations and structural amplifications fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2 ) occur in multiple types of cancer 1 . However, clinical responses to FGFR inhibitors have remained variable 1–9 , emphasizing the need better understand which alterations are oncogenic therapeutically targetable. Here we apply transposon-based screening 10,11 tumour modelling mice 12,13 find truncation exon 18 (E18) Fgfr2 is a potent driver mutation....