Potential Cellular Target for Eliminating Bone Breakdown in Osteoporosis Identified

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. Led by faculty from the Perelman School of Medicine at the University of Pennsylvania, a rodent study showed that bone marrow adipogenic lineage precursors (MALPs) play a distinct role in the way bones remodel themselves. Their study was published in the Journal of Clinical Investigation.

"Discovering new cellular and molecular mechanisms to control bone turnover will enable fine-tuning of existing therapies or design of novel therapeutics," said the study's senior author, Ling Qin. "For example, with the advance of gene-editing technology and novel cell-specific delivery approaches, in the future it would be possible to regulate MALP behavior as a therapy for bone disorders like osteoporosis."

Recent studies by Qin and her fellow researchers 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, Qin and her colleagues found that MALPs secrete RANKL, a protein essential for forming osteoclasts, at a high level.

With that information, the 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 and vertebrae, something the researchers qualified as "a drastic increase" compared to typical mouse bone mass.

"By identifying what appears to be the full function of MALP cells, we believe that we have uncovered an extremely promising target that would never have been considered before," Qin said. "If their RANKL secretions can be reliably disabled, it could rebalance bone remodeling in people with osteoporosis and allow for osteoblasts and osteocytes to 'catch up.'"