# Osteocyte peri-lacunar/canalicular remodeling in maternal bone adaptation

> **NIH NIH R56** · UNIVERSITY OF PENNSYLVANIA · 2024 · $228,125

## Abstract

Project Summary
During pregnancy and lactation, the female skeleton undergoes significant bone loss and bone microstructure
deteioration to provide calcium for fetal/infant growth. While weaning induces substantial bone recovery,
reproduction-induced bone loss is only partially recovered after weaning. Our objective in the last funding cycle
was to uncover protective mechanisms behind the lower fracture risk in women with histories of reproduction
and lactation. Using a rat model, we demonstrated that structural adaptation of the maternal skeleton during
pregnancy and lactation exerted a protective effect against estrogen deficiency-induced bone loss later in life.
Moreover, we discovered enhanced responsiveness to external loading in the rat maternal bone both during
lactation and later when subjected to estrogen deficiency by ovariectomy (OVX). During lactation, osteocytes
(Ocys) are known to actively remodel their surrounding matrix via perilacunar-canalicular remodeling (PLR).
Intriguingly, we also discovered enhanced Ocy PLR in the maternal bone post OVX, which appeared to be a
result of “memory” or reactivation of Ocys’ PLR response during lactation. The activated PLR during lactation
and post OVX leads to an enlarged lacunar-canalicular system (LCS) and an altered microenvironment of
Ocys. Using a multiscale poroelastic model of the LCS, we further demonstrated that the PLR-induced
alterations in the Ocy pericellular environment would amplify the mechanical and biochemical signal
transduction to Ocys, which could in turn enhance mechanical adaptation of maternal bone to maintain its
load-bearing function. These new and exciting findings provide a strong scientific premise for our central
hypothesis that Ocy PLR-mediated skeletal adaptation increases Ocys’ mechano-sensing, which in turn
enhances the mechano-response of maternal bone during lactation and post OVX. The objective of this
renewal continues to be defining maternal bone adaptation mechanisms during challenging physiological
events such as lactation and menopause. However, our focus advances from bone micro- and ultra-structural
mechanisms (in the last funding cycle) to cellular mechanisms behind maternal bone adaptation and skeletal
health (in this renewal). A cutting-edged imaging platform allows us to directly quantify mechano-sensitivity of
the Ocy network by measuring in situ Ca2+ oscillations in mechanically loaded bones. In the Aim 1, we will
establish the causal role of osteocyte PLR as an important mechanism to regulate bone mechano-sensitivity.
In the Aim 2, by employing osteocyte fate mapping in a mouse model, we will for the first time interrogate the
mechano-responses between osteocytes with and without exposure to prior lactation or lactation-associated
hormonal changes within the same bone. The proposed research project will define a novel and critical
function of ostecytes through PLR to regulate the balance between mineral resorption and mechanical integrity
of th...

## Key facts

- **NIH application ID:** 11175789
- **Project number:** 2R56AR071718-06A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Xiaowei Sherry Liu
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $228,125
- **Award type:** 2
- **Project period:** 2017-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11175789

## Citation

> US National Institutes of Health, RePORTER application 11175789, Osteocyte peri-lacunar/canalicular remodeling in maternal bone adaptation (2R56AR071718-06A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11175789. Licensed CC0.

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