Bone circuitry and interorgan skeletal crosstalk

Mone Zaidi, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Se-Min Kim, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Mehr Mathew, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Funda Korkmaz, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Farhath Sultana, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Sari Miyashita, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Anisa Azatovna Gumerova, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Tal Frolinger, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Ofer Moldavski, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Orly Barak, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Anusha Pallapati, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Satish Rojekar, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
John Caminis, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Yelena Ginzburg, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Vitaly Ryu, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Terry F. Davies, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Daria Lizneva, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Clifford J. Rosen, MaineHealth Institute for Research, Scarborough, ME.Follow
Tony Yuen, The Mount Sinai Bone Program, Departments of Pharmacological Sciences and of Medicine, and Center of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.

Document Type

Article

Publication Date

1-19-2023

Institution/Department

MaineHealth Institute for Research

Journal Title

eLife

MeSH Headings

Humans; Bone and Bones; Osteoblasts (metabolism); Osteoclasts (metabolism); Osteocytes (metabolism); Pituitary Hormones (metabolism)

Abstract

The past decade has seen significant advances in our understanding of skeletal homeostasis and the mechanisms that mediate the loss of bone integrity in disease. Recent breakthroughs have arisen mainly from identifying disease-causing mutations and modeling human bone disease in rodents, in essence, highlighting the integrative nature of skeletal physiology. It has become increasingly clear that bone cells, osteoblasts, osteoclasts, and osteocytes, communicate and regulate the fate of each other through RANK/RANKL/OPG, liver X receptors (LXRs), EphirinB2-EphB4 signaling, sphingolipids, and other membrane-associated proteins, such as semaphorins. Mounting evidence also showed that critical developmental pathways, namely, bone morphogenetic protein (BMP), NOTCH, and WNT, interact each other and play an important role in postnatal bone remodeling. The skeleton communicates not only with closely situated organs, such as bone marrow, muscle, and fat, but also with remote vital organs, such as the kidney, liver, and brain. The metabolic effect of bone-derived osteocalcin highlights a possible role of skeleton in energy homeostasis. Furthermore, studies using genetically modified rodent models disrupting the reciprocal relationship with tropic pituitary hormone and effector hormone have unraveled an independent role of pituitary hormone in skeletal remodeling beyond the role of regulating target endocrine glands. The cytokine-mediated skeletal actions and the evidence of local production of certain pituitary hormones by bone marrow-derived cells displays a unique endocrine-immune-skeletal connection. Here, we discuss recently elucidated mechanisms controlling the remodeling of bone, communication of bone cells with cells of other lineages, crosstalk between bone and vital organs, as well as opportunities for treating diseases of the skeleton.

Link to Full Text

Share

COinS