Christian Jacome-Galarza – A Bone to Pick with Osteoclasts

Christian Jacome-Galarza – A Bone to Pick with Osteoclasts

Dr Christian Jacome-Galarza was born and raised in Mexico. Here he also received his Undergraduate degree in Pharmaceutical Sciences and his Master’s degree in Clinical Biomedicine, both from the University of the Americas-Puebla. After completing his Master’s research, he relocated to the U.S. where he received his PhD in Immunology from the University of Connecticut Health Center.  Currently, Dr Christian Jacome-Galarza is a research fellow in the Department of Orthopedics at Brigham and Women’s Hospital in Boston.

As an avid sportsman himself, enjoying activities such as hiking, skiing and soccer, he understands the devastation that diseases that limit physical ability can have. Through research such as his own, it is hoped that the damage caused by diseases such as arthritis can be halted or completely prevented, giving patients the ability to embrace a more active lifestyle. He strives to ensure patients with these conditions will continue to walk tall but not walk alone.

Inflammatory Statements

Inflammatory arthritis (IA) is the term used to describe a group of conditions that result from an overactive immune system leading to chronic inflammation. A key feature between these conditions is the manifestation of inflammation of joints, resulting in pain and stiffness. Although joints are the most commonly affected IA can affect other connective tissues including the lungs, heart, eyes, skin and other organs. Inflammation in healthy individuals is a normal process by which immune cells are recruited, it is limited and protective in the short term. Prolonged inflammation, occurring in these conditions, when the immune system does not self-regulate correctly can lead to damage which can be irreversible. Not only does inflammation occur for extended periods it occurs where it is not necessary. In addition to the pain and stiffness caused by IA, patients can experience fatigue and overtime can have limited movement and mobility.

A Balancing Act

The health of our bones is maintained according to a balancing act between two sets of cells – osteoclasts and osteoblasts. Osteoclasts (OC) along with osteoblasts form part of a partnership of cells responsible for balancing our bone remodeling. Bone remodeling is the continuous process of synthesis and destruction and is key in giving bone its mature structure and helps to maintain normal calcium levels throughout the body. Osteoclasts breakdown bone whilst osteoblasts rebuild it.  Resorption, of bone by OCs releases calcium into the bloodstream which is used to meet the body’s metabolic needs. Simultaneously this process permits the bone—which is inhibited by its inorganic component from growing by cellular division like other tissues—to modify size and shape  necessary as it grows to adult proportions. OCs develop in the bone marrow and are usually found in the pits in the bone surface. 

Rogue Osteoclasts

Dr Jacome-Galarza has devoted his research to studying the biology of osteoclasts and how they contribute to conditions affecting joints such as IA. He questions: why are the same cells (OCs) that are so critical for helping to build the bone marrow cavity, erupting and shaping teeth, and maintaining healthy bones, so destructive in inflammatory conditions and diseases? In patients with inflammatory arthritis, OCs appear in joints, an anatomical site in which they do not normally occur. Their presence contributing to damage in the joint as the balance of the bone remodeling process is disrupted.

A number of factors need to be taken into account when addressing the role of OCs in disease presentation and progression. What are the cell signals, conditions, and mechanisms of regulation that are required for such contrasting outcomes between healthy individuals and patients with joint disease? What possibilities exist to prevent or repair such damage? These are the questions that continue to inspire Dr Jacome-Galarza to pursue his studies on the cellular origins and regulatory mechanisms of bone and cartilage destructive cells in arthritis.

IA can be controlled to an extent using medication. Early intervention and treatment can put patients into remission, although this is not always achieved no matter how early intervention occurs. More commonly people with inflammatory arthritis will initially experience intermittent symptoms (flare-ups) of their condition. These periods are interspersed with periods of resolution, when they do not experience symptoms. However, in most, the condition will eventually become chronic and ongoing medical care is needed. Currently, not all patients treated with available therapeutics prevent this damage.

Redress the Balance

Dr Jacome-Galarza is using his expertise and applying his ANRF grant to fund research which looks at how OCs are formed, genetic factors that induce their activation and how they cause tissue destruction. This project emerged based on his recent discoveries that OCs are cells that normally originate from different progenitors under homeostatic conditions [Jacome-Galarza et al. Nature 2019;568(541-545)]. However, during inflammatory conditions, like those observed in arthritis, OCs are generated in anatomical sites where they do not normally occur, raising the question of the cellular sources of OCs and consequently possible alternative regulatory pathways to control bone destruction in inflammatory arthritis.

He will be focusing on investigating the specific cellular sources of OCs and other myeloid cells (myelopoiesis in the broadest sense of the term is the production of bone marrow and of all cells that arise from it, namely, all blood cells). Of particular relevance will be the transcriptional regulatory mechanisms (mechanism involved in the expression of relevant genes) and how these mechanisms control the function of these cells in IA. The research will specifically look at OC precursor cells, known as macrophages and monocytes, that under certain conditions give rise to OCs and how they form OCs in the inflamed joints. Basically, the research will be addressing what makes OCs in arthritic joints different to normal OCs.

Understanding the complexity of OCs and the myeloid system in homeostasis and inflammation will hopefully allow Dr Jacome-Galarza to develop novel therapeutic targets to prevent bone and cartilage erosions in inflammatory arthritis.   

This ANRF grant has provided Christian with the opportunity to explore such intriguing yet unanswered scientific questions. Dr Jacome-Galarza believes that the work he will be able to undertake as an ANRF scholar will set the foundation for his future scientific career in the field of arthritis and inflammation.

 

 


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ANRF
Article Author
Arthritis National Research Foundation
arthritisresearch@curearthritis.org

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

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