Many athletes take painkillers regularly after intense workout sessions. The reason being, any muscle injury, inflammation, soreness, stiffness and aches can be handled with these medicines. But a new study suggests that these anti-inflammatory non-steroidal drugs often harm the muscles rather than doing any good. A Stanford Medicine study supports this view and proposes a new study, based on the inflammatory component to treat muscle degeneration with muscle stem cells.

The stem cells in muscles are scattered across the skeletal muscle tissue. They remain inactive until they are divided by stimulation. When our muscles go through an injury or damage, an inflammatory component activates these muscle stem cells, so they start regenerating the tissue.

The team at Stanford suggests that a molecule, Prostaglandin E2 or PGE2, gets released when the muscle sends the inflammatory signal. This component stimulates the repairing process by aiming at the EP4 receptor, located on the surface of muscle stem cells. The muscle stem cells division is caused by the interaction between PGE2 and EP4, which leads to muscle tissue regeneration.

Dr. Helen Blau, the senior author of the study, said, “Traditionally, inflammation has been considered a natural, but sometimes harmful, response to injury. But we wondered whether there might be a component in the pro-inflammatory signaling cascade that also stimulated muscle repair. We found that a single exposure to prostaglandin E2 has a profound effect on the proliferation of muscle stem cells in living animals. We postulated that we could enhance muscle regeneration by simply augmenting this natural physiological process in existing stem cells already located along the muscle fiber.”

They have conducted a study on a mice model and it reveals that the PGE2 is increased by injuries and that in turn increases the expression of the EP4 receptor. This incident leads the team to the idea of treating the mice with PGE2 pulse, so they can stimulate the muscle stem cells to repair the damage.

Dr. Adelaida Palla, the co-first author explained, “When we gave mice a single shot of PGE2 directly to the muscle, it robustly affected muscle regeneration and even increased strength. Conversely, if we inhibited the ability of the muscle stem cells to respond to naturally produced PGE2 by blocking the expression of EP4 or by giving them a single dose of a nonsteroidal anti-inflammatory drug to suppress PGE2 production, the acquisition of strength was impeded.”

The research clearly shows that painkillers can make the situation worse. Additionally, it also suggests that the molecule; PGE2 can be the natural element to enhance muscle regeneration. Dr. Blau is hopeful that future studies will show more encouraging results with PGE2.  “Our goal has always been to find regulators of human muscle stem cells that can be useful in regenerative medicine. It might be possible to repurpose this already FDA-approved drug for use in muscle. This could be a novel way to target existing stem cells in their native environment to help people with muscle injury or trauma, or even to combat natural aging,” added Dr. Blau.

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Temporomandibular joint or more commonly referred to as TMJ, is a condition that many suffer from on a global scale. A recent study found out that approximately 10 million people, women being a majority in the US are victims to this disorder.

So what is the temporomandibular joint?
The joint that links your jaw to the temporal bones of your skull, which are located right in front of your ear, is known as your temporomandibular joint. It acts like an axis that allows movements of your jaw that enables you to speak, chew and yawn.

If you are having trouble with your jaw and the controlling muscles in your face, it is called temporomandibular disorders or TMD. The cause of this disorder is not clearly known or defined. Probable symptoms of TMD, which dentists believe could actually be a result of issues in the jaw muscles or with the parts of the joint itself.

Acute ache and soreness are often triggered by TMD that may affect both sides of your face. This may subsequently lead to various other indications like concentrated discomfort in the jaw, face and head; inconvenience in gulping and talking and faintness. The condition may be temporary or possibly last for several years. It is a common occurrence between the ages of 20 to 40.

Made of fibrocartilage, TMJ in a healthy state helps the jaw to function smoothly by acting as a cushion. Nevertheless, the cartilage is not equipped with the capability to repair or renew. Hence, all the available treatment or surgery does, is disguise the indicators but not actually repair the essential impairment of the joint.

Published in Nature Communications under “Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury,” a research team at Columbia University’s College of Dental Medicine (USA) carried out a cell culture studies as well as clinical trials on animals, acknowledged that stem cells inside the TMJ possessed the potential to develop cartilage and bone. Further investigations by the research team presented that Wnt, a protein, with its signalling activity led to the diminution of these fibrocartilage stem cells (FSCSs) in animals. As a result of this, it instigated significant weakening of the cartilage on introducing an accepted inhibitor of Wnt into the animals’ impaired TMJ stimulated development and recuperation of the joint.

“This is very exciting for the field because patients who have problems with their jaws and TMJs are very limited in terms of clinical treatments available,” said Mildred C. Embree, DMD, PhD, assistant professor of dental medicine at Columbia and lead author of the study. Dr. Embree’s team, the TMJ Biology and Regenerative Medicine Lab, conducted the research with colleagues including Jeremy Mao, DDS, PhD, the Edwin S. Robinson Professor of Dentistry (in orthopedic surgery) at Columbia.[1]

The next step of the investigation is to explore options of suitable Wnt inhibitors that may be tried under clinical conditions. In a university press release, Jeremy Mao, a co-author on the paper, talked about the implications of these results. “They suggest that molecular signals that govern stem cells may have therapeutic applications for cartilage and bone regeneration. Cartilage and certain bone defects are notoriously difficult to heal.”[2]

In the long run, Dr. Embree and her team say the outcomes could spearhead eventual strategies for mending fibrocartilage in other joints, including the knees and vertebral discs. “Those types of cartilage have different cellular constituents, so we would have to really investigate the molecular underpinnings regarding how these cells are regulated,” the researcher said.[3]

Sources:

• http://www.dentistryiq.com/articles/2016/10/tmj-stem-cells-used-to-repair-cartilage-in-the-joint.html
• https://www.ncbi.nlm.nih.gov/pubmed/26123357
• http://www.webmd.com/oral-health/guide/temporomandibular-disorders-tmd#1
• https://blog.cirm.ca.gov/2016/10/14/stem-cell-stories-that-caught-our-eye-relief-for-jaw-pain-vitamins-for-ipscs-and-alzheimers-insights/

[1] Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury – Mildred C. Embree, Mo Chen, Serhiy Pylawka, Danielle Kong, George M. Iwaoka, Ivo Kalajzic, Hai Yao, Chancheng Shi, Dongming Sun, Tzong-Jen Sheu, David A. Koslovsky, Alia Koch & Jeremy J. Mao

[2] Stem cells from jaw bone help repair damaged cartilage – Columbia University College of Dental Medicine, October 10, 2016

[3] TMJ stem cells used to repair cartilage in the joint – Posted by DentistryIQ Editors, October 12, 2016

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