A new study has determined that lysosomal acid lipase (LAL), a deficiency of which causes lysosomal acid lipase deficiency (LAL-D), is an important component of cellular energy metabolism, particularly in the cytodifferentiation of human periodontal ligament (HPDL) cells.

The study, published in Biochemical and Biophysical Research Communications, found that a deficiency of LAL in HDPL cells resulted in less oxidative phosphorylation (OXPHOS) and reduced production of ATP.

“The mechanisms underlying the suppression of the cytodifferentiation of human periodontal ligament (HPDL) cells mediated by LIPA/LAL are still not fully elucidated,” the authors wrote. “Therefore, we aimed to investigate the regulation mechanisms of the cytodifferentiation of HPDL cells by LAL in terms of energy metabolism. In this study, we elucidated that LAL supports the cytodifferentiation of HPDL cells by mediating the adequate amount of energy through the OXPHOS-related bioenergetic pathway.”


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The research team osteogenically induced HPDL cells with and without Lalistat-2, which is an inhibitor of LAL. They measured lipid droplet catalysis to fatty acids and the resulting ATP production via OXPHOS and glycolysis in both conditions.

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Without Lalistat 2, lipid metabolism, mRNA expression, and energy generation were significantly upregulated during the cytodifferentiation of HPDL cells. However, in the presence of Lalistat-2, ATP production, lipid droplet utilization, and mRNA expression were reduced.

The periodontal ligament is comprised of heterogeneous cell populations and contains mesenchymal stem cells that can differentiate into osteoblasts and cementoblasts. During periodontal ligament cytodifferentiation, the OXPHOS pathway is upregulated, suggesting that sufficient energy metabolism during this process could regenerate periodontal tissues.

In LAL-D, bone volume and osteoblast number are reduced, increasing the risk of bone fractures. In this study, the authors found that LAL supports HPDL cell cytodifferentiation by mediating the OXPHOS bioenergetic process, shedding light on possible implications of LAL deficiency in diseases such as LAL-D.

Reference

Nantakeeratipat T, Fujihara C, Nogimori T, et al. Lysosomal acid lipase regulates bioenergetic process during the cytodifferentiation of human periodontal ligament cells. Biochem Biophys Res Comm. Published online June 25, 2023. doi:10.1016/j.bbrc.2023.04.041