Skip Navigation
request an appointment my chart notification lp musc-logo-white-01 facebook twitter youtube blog find a provider circle arrow
MUSC mobile menu

STAT

An MUSC blog
Keyword: rheumatology

The Musculoskeletal Institute at MUSC Health brings orthopaedics, rheumatology and endocrinology specialists under one roof to treat an array of bone and joint disorders as well as metabolic bone diseases and osteoporosis.

This multidisciplinary care model offers care and convenience benefits to patients: The team’s depth of expertise in musculoskeletal care makes the institute uniquely capable of coordinating the care of patients with complex conditions. And patients don’t have to travel to see the specialists they need—they can get all of their care in one place, saving them time and energy.

Treating Hip Pain: What Multidisciplinary Looks Like

The institute’s multi-specialty approach ensures a smooth process for both patients and doctors. Patients can easily get the services they need, and physicians can seamlessly coordinate that care.

“Our advantage as a functional unit for patient care is that the physicians within those three groups interchange and freely move patients among one another based upon the diagnoses and the needs of the patients,” says  Vincent Pellegrini, M.D., chief of the Musculoskeletal Institute and chair of the department of orthopaedics at MUSC.

Consider a patient with hip pain, who makes an appointment with Dr. Pellegrini. If he determines that a patient’s pain originates from the back, he can simply walk around the corner to a spine surgeon colleague.

“The spine surgeon would then see that patient,” explains Dr. Pellegrini. “And he may decide that day that the patient really doesn't need an operation but might benefit from injection therapy.”

The coordination continues from there: “The spine surgeon would then walk around the corner and take that patient to see a physiatrist or a physical medicine physician, who might then do a therapeutic and diagnostic injection.”

Diagnostic tests, evaluation by multiple specialists and treatment: All this could happen in the same space, on the same day, even though the patient came in for hip pain and it turned out to be a back condition. These are not “what-if” scenarios—stories like this happen daily at the Musculoskeletal Institute at MUSC Health.

Orthopaedics, Endocrinology and Rheumatology: A Triad of Care Focus

The Musculoskeletal Institute combines orthopaedics, endocrinology and rheumatology for a reason: These disciplines frequently cross over and require complex care decisions, such as physical rehabilitation.

Patients who benefit from this type of care can include:

  • An orthopaedic patient who thought he or she needed surgery but could benefit from a joint injection and a rehabilitative specialist consult
  • A patient with rheumatoid arthritis who is having severe hand pain, who could benefit from consulting with a hand surgeon and a hand therapist
  • A patient with osteoporosis who has been using Fosamax® for a long time and has unique fractures that require the collaboration of an endocrinologist (to adjust the medication and dosing) and an orthopaedic surgeon (to surgically treat the problem)
  • A patient with hip or knee arthritis who needs an orthopaedic surgeon to address inflammatory arthritis and a rheumatologist to help adjust the medication before surgery

At many centers, all of those appointments would need to be on separate days, with separate specialists. At the Musculoskeletal Institute, we bring together an extensive team to care for a wide swath of people—in a more effective, efficient way.

“With many of our patients, it can take a village to have all of the resources needed to take care of certain problems that are a little more unusual,” says Dr. Pellegrini.

Hip Pain, Osteoporosis and More: Patient and Physician Benefits

The Musculoskeletal Institute has a patient-centric focus, resulting in care that’s improved, coordinated and timely. Dr. Pellegrini says these benefits extend to referring physicians as well—particularly for complicated cases that could use an extra set of eyes from a different specialist.

“I believe most referring physicians are primarily interested in taking care of their patients in a way that’s efficient and expedient,” he says. “Because we put an array of resources under one roof, it allows us to take care of some of the more complicated patient needs that can overwhelm a smaller practice with fewer resources. Our team approach can be very beneficial in certain patient situations.”

For more information, contact Dr. Pellegrini at pellegvd@musc.edu.
 

Anti-fibrotic effects of M10 in a mouse model of interstitial lung disease

Caption: Lung tissue isolated from mice that received bleomycin is characterized by extensive infiltration of inflammatory cells, thickening of the alveolar walls, and multiple fibrotic lesions with excessive amounts of extracellular matrix proteins (left). Lung tissue from mice receiving bleomycin + M10 shows significant reduction of cellular infiltrates, decreased thickness of alveolar septa, and reduced accumulation of extracellular matrix proteins (right). Images courtesy of Galina S. Bogatkevich, M.D., Ph.D. Reproduced from Translational Research (http://www.translationalres.com), Volume 170, April 2016, Pages 99–111, with permission from Elsevier.

Summary: Investigators at the Medical University of South Carolina report preclinical findings showing that the M10 peptide reduces collagen production and reverses fibrotic damage due to systemic sclerosis (SSc)–associated interstitial lung disease (ILD) in the April 2016 issue of Translational Research. ILD is one of the deadliest complications of SSc, a chronic autoimmune disease characterized by vasculopathy, autoimmunity, and excessive collagen production and deposition. Lung fibrosis carries a high risk of morbidity/mortality in SSc patients.

 

The results of preclinical studies by investigators at the Medical University of South Carolina (MUSC) reported in the April 2016 issue of Translational Research suggest that the M10 peptide could help protect against fibrotic damage in patients with systemic sclerosis, particularly in those who develop interstitial lung diseases (ILD), its deadliest complication.

Fibrotic diseases, which are characterized by excessive scarring due to overproduction by fibroblasts of collagen or extracellular matrix, account for more than 45% of U.S. deaths—more than cancer—and are estimated to cost $10 billion annually. Despite the prevalence of fibrotic diseases, only a handful of anti-fibrotic agents have been approved by the U.S. Food and Drug Administration, and none is available for systemic sclerosis.

In many ways, systemic sclerosis is the quintessential fibrotic disease, since its scarring can damage any part of the body. “Systemic sclerosis is often more than skin deep, affecting the gastrointestinal tract, the lungs, the heart, the kidneys, and the blood vessels, so it is a model for many other more prevalent fibrotic diseases,” says Richard M. Silver, M.D., Director of the Division of Rheumatology and Immunology at MUSC and a co-author on the article. “Whereas there may be 300,000 Americans with scleroderma/systemic sclerosis, millions of others suffer from fibrosis of these other organ systems.”

M10 is a ten-amino acid peptide formed from the natural cleavage of the receptor tyrosine kinase MET by the caspase 3. MET, also known as hepatocyte growth factor receptor, is thought to protect against injury and fibrosis, but the mechanisms by which it does so have remained unclear.

The MUSC investigators showed that M10 could protect against fibrotic injury in a bleomycin-induced model of ILD and that its anti-fibrotic effects are likely due to its modulation of the transforming growth factor beta 1 (TGF-?1) pathway. TGF-?1 is a cytokine that has been implicated in inflammation and fibrosis.

“We observed that treatment with M10 by intraperitoneal injection markedly improved bleomycin-induced lung fibrosis in mice, suggesting that the M10 peptide may have potential for use in the treatment of scleroderma-associated interstitial lung disease and other forms of pulmonary fibrosis, for example, idiopathic pulmonary fibrosis,” says Galina S. Bogatkevich, M.D., Ph.D., senior author on the Translational Research article. Lead authors for the article are Ilia Atanelishvili, M.S., of MUSC and Yuichiro Shirai, M.D., Ph.D., who holds a dual appointment at MUSC and the Nippon Medical School.

When instilled intratracheally, bleomycin induces fibrotic changes in the lungs, including peribronchial and interstitial infiltration of inflammatory cells, thickening of alveolar walls, and the development of numerous fibrotic lesions with excess deposition of extracellular matrix protein. Using this bleomycin-induced model of lung fibrosis, the MUSC investigators evaluated the anti-fibrotic effects of M10, using a scrambled peptide as a control. The scrambled peptide had the same ten amino acids as M10 but arranged in a different order. Fibrosis was quantitated using the Ashcroft scale, which ranges from 0 (normal) to 8 (totally fibrotic).

As expected, mice receiving bleomycin plus a scrambled peptide showed greater than eight times more lung fibrosis than controls receiving saline and scrambled peptide (Ashcroft scores, 5.63±1.72 vs. 0.69± 0.35). However, Ashcroft scores dropped to 1.67±1.01 when mice were administered both bleomycin and M10, suggesting the anti-fibrotic potential of this peptide.

Because M10 was given on the same day as bleomycin, its anti-fibrotic effects are considered preventive. To establish the therapeutic anti-fibrotic efficacy of M10, Bogatkevich and her MUSC colleagues are planning experiments in which M10 will be administered a week after the instillation of bleomycin, when fibrotic damage has already occurred. If these additional experiments suggest therapeutic efficacy, Bogatkevich hopes to find an industry partner to help take M10 forward into clinical trials.  

Many researchers speculate that there is a final common pathway to fibrosis in many different organ systems. If an anti-fibrotic agent is demonstrated to be effective in systemic sclerosis, which can affect many different organs, it could potentially hold promise for treating fibrotic disease that is confined to particular organ systems as well.

Bogatkevich and the other MUSC investigators also performed in vitro studies to assess the efficacy of M10 in decreasing abnormal collagen production/deposition and to shed light on the mechanism by which it does so. Skin and lung fibroblasts were obtained from three deceased patients with systemic sclerosis with confirmed lung involvement. As expected, these fibroblasts showed high levels of collagen production. Incubation of these fibroblasts with M10 reduced collagen expression in a dose-dependent manner. M10 likewise reduced collagen production induced in normal cells by administration of TGF-?1 without affecting baseline collagen levels.

These findings suggest that the anti-fibrotic effects of M10 may rely on its suppression of the TGF-?1 pathway. Indeed, protein interaction assays showed that M10 likely achieves such suppression by interacting with the Smad2 protein, thereby preventing it from binding to Smad3, which is necessary for the downstream inflammatory effects of the TGF-?1 pathway.
 

Subscribe to Progressnotes

Submit a Story Idea


Current Issue of Progressnotes

Digital EditionPDF | Home

Progressnotes - Spring 2017 cover thumb

Back Issues of Progressnotes

past issues of progressnotes