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Researchers Discover Potential Cellular Targets To Eliminate Osteoporotic Bone Destruction

New research reveals cell types that govern the way bone is formed and maintained, opening up potential targets for future treatments for bone disorders such as osteoporosis. A rodent study led by a faculty member at the University of Pennsylvania’s Perelman School of Medicine showed that bone marrow adipogenic precursors (MALPs) play a clear role in bone remodeling. Because deficiencies in this process are an important issue in osteoporosis, treatments that use these MALP cells to better regulate bone remodeling may lead to better treatment.This study was published in Clinical research journal..

Discovering new cellular and molecular mechanisms for controlling bone turnover allows us to fine-tune existing therapies and design new therapies. For example, advances in gene editing technology and new cell-specific delivery approaches will allow in the future to regulate the behavior of MALP as a treatment for bone disorders such as osteoporosis. “

Ling Qin, PhD, lead author of research, associate professor of orthopedics

Maintaining healthy bone is the balance between osteoblasts, which secrete the materials needed to form new bone, and osteoclasts, which absorb the material of old bone and give way to new bone. If this balance is disturbed in any way, bones can become unhealthy. In osteoporosis, overactive osteoclasts eat up bone faster than it can reshape, resulting in low bone density and increased susceptibility to fractures.

A common consensus among scientists is that fully formed bone cells, osteoblasts and osteoocytes, initiate the production of osteoclasts to initiate bone remodeling. It was that. On the other hand, the role of adipocyte lineage cells such as MALP in the regulation of bone resorption is unknown.

At the beginning of 2020, Qin’s group discovered that MALP was abundant in bone. MALP is a precursor of adipocytes that carry fat called lipids into the bone marrow. And a recent study by Hata and her fellow researchers better revealed how MALP appears to consider bone turnover. They showed that MALP was in cell-cell contact with osteoclasts, not osteoblasts or osteoocytes. In addition, Hata and her colleagues used advanced sequencing techniques at the single-cell level to discover that MALP secretes high levels of RANKL, a protein essential for osteoclast formation.

Based on that information, researchers in this study, including lead authors Wei Yu, MD, and PhD, who work as visiting scholars at the University of Pennsylvania, studied mice with RANKL deficiency in MALP. From the first month of life in these mice, researchers found that the density of spongy components in long bones (such as the femur) and vertebrae was 60-100% higher. This was considered a “dramatic increase” compared to typical mouse bone mass. ..

Since osteoblasts and osteoocytes continue to function as usual, it appears that MALP and its RANKL secretions have been identified as the main drivers of osteoclast function and existing bone resorption. ..

“By identifying what appears to be the full functioning of MALP cells, we believe we have discovered a very promising target that was previously unthinkable,” said Hata. “If we can ensure that RANKL secretion is abolished, we may be able to rebalance bone remodeling in people with osteoporosis and allow osteoblasts and bone cells to” catch up. ” “

These findings are more effective for Jaimo Ahn, MD, and PhD, co-authors of Qin, a former faculty member at the University of Pennsylvania, now responsible for orthopedic trauma at the University of Michigan, and vice-chairman of orthopedics. I believe it will be very helpful in rebuilding bones. “An exciting future step for clinical application is to target MALP in a timely and therapeutic manner and test how they simultaneously reduce bone resorption and increase bone formation.” Said Anne.

Source:

University of Pennsylvania School of Medicine

Journal reference:

Yu, W. , et al. (2020) Bone marrow adipogenic precursors (MALPs) promote osteoclast formation in bone remodeling and pathological bone loss. Clinical research journal. doi.org/10.1172/JCI140214.

Researchers Discover Potential Cellular Targets To Eliminate Osteoporotic Bone Destruction

Source link Researchers Discover Potential Cellular Targets To Eliminate Osteoporotic Bone Destruction

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