The Incidence and Severity of Medication Related Osteonecrosis of the Jaws is Similar in Male and Female Mice.

Background: Medication related osteonecrosis of the jaws (MRONJ), a rare side-effect of antiresorptive medications, is described as exposed bone in the oral cavity that lasts for at least 8 weeks. Most studies report a female predilection for MRONJ; these findings could be due to the increased use of antiresorptives in females, or due to inherent differences between male versus female patients.

Purpose: The purpose of this study was to measure and compare the incidence and severity of osteonecrosis of the jaws (ONJ) between male and female mice.

Epigenetic Regulation of NGF-Mediated Osteogenic Differentiation in Human Dental Mesenchymal Stem Cells.

Nerve growth factor (NGF) is the best-characterized neurotrophin and is primarily recognized for its key role in the embryonic development of the nervous system and neuronal cell survival/differentiation. Recently, unexpected actions of NGF in bone regeneration have emerged as NGF is able to enhance the osteogenic differentiation of mesenchymal stem cells. However, little is known regarding how NGF signaling regulates osteogenic differentiation through epigenetic mechanisms.

The ERα/KDM6B regulatory axis modulates osteogenic differentiation in human mesenchymal stem cells.

Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic treatment of postmenopausal osteoporosis, induces osteogenesis by activating the estrogen receptor signaling pathway and upregulating the expression of osteogenic genes, such as bone morphogenetic proteins (BMPs). The epigenetic regulation of estrogen-mediated osteogenesis, however, is still unclear.

Local RANKL delivery improves socket healing in bisphosphonate treated rats.

Medication related osteonecrosis of the Jaws (MRONJ) is a severe complication of antiresorptive and anti-angiogenic medications. Osteoclast inhibition is central in MRONJ pathogenesis. Here, we investigated if local application of RANKL (a key molecule in osteoclast activation) could enhance osteoclast generation and improve extraction socket healing in the presence of bisphosphonates.

Vasculature submucosal changes at early stages of osteonecrosis of the jaw (ONJ).

Osteonecrosis of the jaw (ONJ), a rare, but potentially severe side effect of anti-resorptive medications, presents as exposed bone in the maxillofacial region lasting for at least 8 weeks. While clinical experience and animal models concur in finding that systemic antiresorptive treatment in conjunction with local risk factors, such as tooth extraction or dental disease may lead to ONJ development, the subclinical molecular changes that precede bone exposure remain poorly understood. The identification of these changes is not only important in understanding disease pathophysiology, but could provide potential for treatment development.

Clinically Relevant Doses of Sclerostin Antibody Do Not Induce Osteonecrosis of the Jaw (ONJ) in Rats with Experimental Periodontitis.

Antiresorptive agents, such as bisphosphonates and denosumab, are frequently used for the management of osteoporosis. Indeed, both medications decrease the risk of osteoporotic fractures; however, these medications are associated with rare but potentially severe side effects, such as osteonecrosis of the jaw (ONJ). ONJ, defined as an area of exposed bone in the maxillofacial region that lasts for 8 weeks, often presents with significant pain and infection and can lead to serious complications.

Local vs. systemic administration of bisphosphonates in rat cleft bone graft: A comparative study.

A majority of patients with orofacial cleft deformity requires cleft repair through a bone graft. However, elevated amount of bone resorption and subsequent bone graft failure remains a significant clinical challenge. Bisphosphonates (BPs), a class of anti-resorptive drugs, may offer great promise in enhancing the clinical success of bone grafting.

Osteonecrosis of the jaws (ONJ) in mice after extraction of teeth with periradicular disease.

Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease.

Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.

Unlabelled: Although adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling.

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study.

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ).

Delivery of siRNA via cationic Sterosomes to enhance osteogenic differentiation of mesenchymal stem cells.

Noggin is a specific antagonist of bone morphogenetic proteins (BMPs) that can prevent the interaction of BMPs with their receptors. RNA interfering molecules have been used to downregulate noggin expression and thereby stimulate BMP signaling and osteogenesis. Cationic liposomes are considered one of the most efficient non-viral systems for gene delivery.

Delivery of Phenamil Enhances BMP-2-Induced Osteogenic Differentiation of Adipose-Derived Stem Cells and Bone Formation in Calvarial Defects.

Bone morphogenetic proteins (BMPs) have been widely used for bone repair in the craniofacial region. However, its high dose requirement in clinical applications revealed adverse effects and inefficient bone formation, along with high cost. Here, we report a novel osteoinductive strategy to effectively complement the osteogenic activity of BMP-2 using phenamil, a small molecule that can induce osteogenic differentiation via stimulation of BMP signaling.

OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice.

Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models.

Visible-light-initiated hydrogels preserving cartilage extracellular signaling for inducing chondrogenesis of mesenchymal stem cells.

Hydrogels have a unique opportunity to regenerate damaged cartilage tissues by introducing mesenchymal stem cells (MSCs) in a highly swollen environment similar to articular cartilage. During cartilage development, collagen-cell interactions play an important role in mediating early mesenchymal condensation and chondrogenesis with transforming growth factor-β1 (TGF-β1) stimulation. Here, a hydrogel environment that can enhance cell-matrix interactions and chondrogenesis by stabilizing type-II collagen (Col II) and TGF-β1 into photopolymerizable (methacrylated) chitosan (MeGC) with simple entrapment and affinity binding is demonstrated.

Bisphosphonate uptake in areas of tooth extraction or periapical disease.

Purpose: Bisphosphonates (BPs) are widely used for the management of bone diseases such as osteoporosis and bone malignancy. However, osteonecrosis of the jaws (ONJ) is a serious complication of BP treatment. ONJ lesions mainly occur after extraction of teeth deemed unrestorable or around teeth with active periodontal or periapical disease.

Biomimetic scaffolds facilitate healing of critical-sized segmental mandibular defects.

Objective: To investigate the efficacy of biomimetic PLGA scaffolds, alone and in combination with bone morphogenic protein (BMP-2) and adipose-derived stem cells (ASCs), to heal a critical-sized segmental mandibular defect in a rat model.

Study Design: Prospective animal study.

Methods: ASCs were isolated and cultured from the inguinal fat of Lewis rat pups.

Spontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: a novel ONJ mouse model.

Although osteonecrosis of the jaws (ONJ), a serious complication of antiresorptive medications, was reported a decade ago, the exact mechanisms of disease pathophysiology remain elusive. ONJ-like lesions can be induced in animals after antiresorptive treatment and experimental interventions such as tooth extraction or periapical or periodontal disease. However, experimental induction and manipulation of disease progression does not always reflect clinical reality.

Adipose-derived stem cells and BMP-2 delivery in chitosan-based 3D constructs to enhance bone regeneration in a rat mandibular defect model.

Reconstructing segmental mandiblular defects remains a challenge in the clinic. Tissue engineering strategies provide an alternative option to resolve this problem. The objective of the present study was to determine the effects of adipose-derived stem cells (ASCs) and bone morphogenetic proteins-2 (BMP-2) in three-dimensional (3D) scaffolds on mandibular repair in a small animal model.

The effects of hyperlipidemia on implant osseointegration in the mouse femur.

A high-fat (HF) diet inducing hyperlipidemia has been associated with the pathophysiology of major diseases, such as atherosclerosis and osteoporosis. A HF diet has significant adverse effects on bone, including lower bone density, volume, and strength. Statins, drugs that lower serum cholesterol levels have beneficial effects on bone metabolism.

RANKL inhibitors induce osteonecrosis of the jaw in mice with periapical disease.

Antiresorptive medications are essential in treating diseases of pathologic osteoclastic bone resorption, including bone cancer and osteoporosis. Bisphosphonates (BPs) are the most commonly used antiresorptives in clinical practice. Although inhibition of bone resorption is important in regulating unwanted malignant and metabolic osteolysis, BP treatment is associated with potential side effects, including osteonecrosis of the jaws (ONJ).

Diverse osteoclastogenesis of bone marrow from mandible versus long bone.

Background: Mandibles (MB) and maxillae possess unique metabolic and functional properties and demonstrate discrete responses to homeostatic, mechanical, hormonal, and developmental stimuli. Osteogenic potential of bone marrow stromal cells (BMSCs) differs between MB versus long bones (LB). Furthermore, MB- versus LB-derived osteoclasts (OCs) have disparate functional properties.

Bone morphogenetic protein-2-impregnated biomimetic scaffolds successfully induce bone healing in a marginal mandibular defect.

Objectives/hypothesis: To test the osteoregenerative potential and dosing of bone morphogenetic protein-2 (BMP-2)-impregnated biomimetic scaffolds in a rat model of a mandibular defect.

Study Design: Prospective study using an animal model.

Methods: Varied doses of BMP-2 (0.

Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice.

Osteonecrosis of the jaw (ONJ) is a well-recognized complication of antiresorptive medications, such as bisphosphonates (BPs). Although ONJ is most common after tooth extractions in patients receiving high-dose BPs, many patients do not experience oral trauma. Animal models using tooth extractions and high BP doses recapitulate several clinical, radiographic, and histologic findings of ONJ.

Composite mandibulectomy: a novel animal model.

Objectives: Segmental mandibular defects can result after the treatment of various pathologic processes, including osteoradionecrosis, tumor resection, or fracture nonunion with sequestration. The variety of etiologies and the frequency of occurrence make the reconstruction of segmental mandibular defects a topic of significant interest. Despite these incentives, a well-established small-animal model of the segmental mandibulectomy, including composite resection, does not exist.