Penn Pharmaceutical Services Ltd.

PHILADELPHIA, Aug. 1, 2024 /PRNewswire/ -- Among the bones of the body, the jaw is unique. During embryonic development, jawbones arise from different types of stem cells compared to bones of the leg or arm. Even some bone disorders have distinctive characteristics when they occur in the jaw. Now, researchers at Penn Dental Medicine are working to uncover the molecular reasons for these differences, with implications that could help in healing following surgery and in the treatment of defects in the maxillofacial region. "Stem cells isolated from the maxilla and mandible have much higher regenerative properties, grow much more rapidly than those that we have from the hip bone, and they need relatively less chemical stimulation for them to form new bone," says Sunday Akintoye, Associate Professor of Oral Medicine at Penn Dental Medicine, who is studying orofacial bone mesenchymal stem cells (MSCs) and their site-specific characteristics and therapeutic applications." Having found that the MSCs in the jaw are key to these special properties, Akintoye's team is working on elucidating the factors that distinguish these MSCs from those in other bones. This information could provide clinicians with tools to replace bone lost to surgery, trauma, and tumors, such as ameloblastoma, which Akintoye has just begun investigating for possible biological indicators of recurrence after surgery. A rare, but rapidly growing tumor, ameloblastoma occurs in the jaw as a result of ameloblasts—the cells that form tooth enamel— growing uncontrollably. The tumor often grows painlessly for a long time in the jaw until eventually, a very large and disfiguring mass is evident. The mass can severely damage the jawbone, and about 10% of the tumors recur, even after surgery. The racial demographics of ameloblastoma patients, as well as whether there are racial disparities in the progression and recurrence of the condition, have not been clear. Akintoye has recently begun to make headway, studying the epidemiology of the condition with an assessment of the literature. In a preliminary analysis, he says the data show that ameloblastoma occurs and recurs more frequently in Black patients than non-Black patients. His team would like to eventually apply their knowledge about oral MSCs to understand ameloblastoma's behavior. "Incorporation of the jaw stem cells into a graft could help promote rapid healing," says Akintoye, "and can help with jaw reconstruction after surgery." Media Contact: Beth Adams, [email protected] SOURCE PENN DENTAL MEDICINE

PHILADELPHIA, July 31, 2024 /PRNewswire/ -- Mast cells are found throughout the body close to blood vessels and are packed with granules containing the immune signaling compound histamine, and enzymes that attack pathogens and promote white blood cell recruitment. When triggered by a perceived threat, mast cells expel their contents. This activity protects against infection and aids healing, but it has also made mast cells infamous for driving allergic asthma and inflammatory skin disorders, such as rosacea and contact dermatitis. Despite their prominence, few researchers study these scarce and difficult-to-work-with cells. Hydar Ali, a professor in the Department of Translational Sciences at Penn Dental Medicine, belongs to a select group who focus on mast cells. His research explores how they function to protect the body and how things can go wrong. "These cells are relatively poorly understood, and yet we've been able to identify some of the most sought-after molecular targets to affect diseases like allergies and asthma that have the potential to kill," Ali says. He and his colleagues discovered a receptor, known as MRGPRX2, that only appears on mast cells. This research led them to find that small proteins called antimicrobial peptides could activate mast cells through MRGPRX2 to harness their protective function and help clear pathogens. In the context of an allergic response, however, he has shown that this receptor drives problematic inflammation. "It's two sides of the same coin," Ali says. More recently, his team has investigated mast cells' role in systemic allergic reactions that can lead patients to stop using the multiple sclerosis drug glatiramer acetate. Their experiments demonstrated that this medication activates MRGPRX2 receptors causing mast cells to expel histamine and their other contents, results suggesting MRGPRX2 inhibitors could treat these reactions and help patients remain on the medication. His lab is also investigating this receptor's role in periodontal disease, an inflammatory condition that damages the gums and connective tissue of the mouth. Their experiments have shown, for example, that mast cells expressing MRGPRX2 become more abundant in chronic periodontitis, the more severe form of the condition. Ultimately, he hopes to study the potential for MRGPRX2 blockers to reduce inflammation in periodontitis. Media Contact: Beth Adams, [email protected] SOURCE PENN DENTAL MEDICINE

PHILADELPHIA, July 29, 2024 /PRNewswire/ -- The tastebuds of the tongue contain bundles of specialized cells bearing sensors that detect chemical attributes of food. Known as taste receptors, these sensors were long believed to reside only on the tongue. Marco Tizzano, an associate professor in the Department of Basic & Translational Sciences at Penn Dental Medicine, was among those who discovered them in many places elsewhere in and on the body. He has since documented taste receptors throughout the airways, especially in the nose, but also the trachea and the lungs, as well as the gums and even dental pulp. These sensors, he and others have found, detect bacterial pathogens and allergens, then alert the innate immune system. Tizzano's research has shown that bitter sensing taste receptors in the nose respond to a compound bacteria use to communicate. These sensors then activate the trigeminal nerve, a cranial nerve that provides sensation to the face, leading to a significant inflammatory response. Bitter taste receptors also show up in the gums. In experiments, Tizzano's research team demonstrated that in gum tissue these receptors actually offer some natural protection against periodontitis, the most severe form of gum disease. After sensing pathogenic bacteria, they trigger the production of antimicrobial peptides to kill the germs. Without these receptors, mice suffered from more damaging periodontitis, the researchers found. In another line of study, Tizzano's lab is looking at odor-detecting receptors found on neurons in dental pulp. When these relatives of the taste sensors detect eugenol, an odor molecule from cloves, they numb the teeth. As someone who looks for connections between disciplines, Tizzano ultimately seeks to use naturally occurring compounds, such as eugenol, to stimulate these receptors in ways that benefit health. Such applications could include a new form of pain relief for dental procedures or a therapy to stifle the microbial growth triggering the inflammation that drives periodontal disease. "I think we are still at the tip of the iceberg," Tizzano says. "There is so much more to discover about these receptors." Media Contact: Beth Adams, [email protected] SOURCE PENN DENTAL MEDICINE