Osteoporosis is the name given to the loss of bone density with age, producing severe consequences in the later stages. The proximate cause is a growing imbalance between the constant activity of osteoblast cells that that create bone and osteoclast cells that break down bone. Researchers here delve into the regulation of osteoclast function, and find a lineage of cells that might be targeted to reduce osteoclast activity in later life. This is a compensatory potential class of therapy, rather than an approach that addresses the root causes of the issue, but nonetheless interesting.
New research has discovered a cell type that governs the way bones form and maintain themselves, opening up a potential target for future therapies for bone disorders like osteoporosis. A rodent study showed that bone marrow adipogenic lineage precursors (MALPs) play a distinct role in the way bones remodel themselves. Defects in this process are the key issue at play in osteoporosis, so a therapy using these MALP cells to better regulate bone remodeling could result in better treatments.
Healthy bone maintenance is a balance between osteoblasts, which secrete the materials necessary to form new bone, and osteoclasts, which absorb old bone material to make way for the new. A disruption in this balance one way or the other can result in unhealthy bone. In the case of osteoporosis, overactive osteoclasts eat away at bone faster than it can be reformed, resulting in bones that are less dense and more susceptible to fracture. The general consensus among scientists was that osteoblasts and osteocytes, the cells within fully-formed bone, were the ones that kicked off the production of osteoclasts to begin the remodeling of bone. On the other hand, the role of adipocyte lineage cells, such as MALPs, in regulating the resorption of bone was not known.
MALPs are the precursors for adipocytes that carry fats, called lipids, inside bone marrow. Recent studies better cleared up how MALPs appear to factor in bone turnover. They showed that MALPs, but not osteoblast or osteocytes, have cell-to-cell contact with osteoclasts. Additionally, using advanced sequencing techniques at a single cell level, researchers found that MALPs secrete RANKL, a protein essential for forming osteoclasts, at a high level.
With that information, researchers studied mice with RANKL deficiencies in their MALPs. From the point those mice turned a month old, the researchers saw 60 to 100 percent higher density of the spongy components of long bones (like the femur) and vertebrae, something the researchers qualified as "a drastic increase" compared to typical mouse bone mass. Since the osteoblasts and osteocytes continued to work as they always do, it would seem that MALPs and their RANKL secretions have been pinpointed as the main driver of osteoclast function and the absorption of existing bone.
Link: https://www.pennmedi...eoporosis-found
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