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 time 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 other kind of cells in regulating the resorption of bone was not known. 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.
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. 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. Earlier in 2020, the team discovered the abundant existence of MALPs within bone. MALPs are the precursors for adipocytes that carry lipids inside bone marrow. And recent studies by Professor Ling Qin and her fellow s 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.
Adipose tissue, is a known producer of cytokines and other molecules possessing cytokine and chemokine.like functions. These include adipokines and growth factors that play an intricate modulation of biological responses at cellular level. With this mechanism, indeed, using advanced sequencing techniques at a single cell level, the researchers found that MALPs secrete at a high level RANK ligand (RANK-L), a protein essential for forming osteoclasts. With that information, the researchers for this study studied mice with RANKL deficiencies in their MALPs. From the point those mice turned a month old, the researchers saw 60-100% 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. 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.
Researchers believes these discoveries could be very useful in more effectively rebuilding bone: an exciting future step, with an eye toward clinical application, would be to target MALPs in a timed and therapeutic fashion to test how well they simultaneously decrease the bone resorption and increase bone formation. Ling Qin, senior associate professor of Orthopaedic Surgery, stated: “Discovering new cellular and molecular mechanisms to control bone turnover will enable fine-tuning of existing therapies or design of novel therapeutics. 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. 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”.
This research is now published in the Journal of Clinical Investigation.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Yu W et al., Qin L. J Clin Invest 2020 Nov 18:140214.
Chen X et al. Front Pharmacol. 2018 Jun 20; 9:647.
Zhong L et al., Qin L. Elife 2020 Apr 14; 9:e54695.
