Bone sialoprotein in bone remodeling: mechanisms of action, context dependence, and evidence related to osteoporosis
- 1Inner Mongolia Medical University College of Traditional Chinese Medicine
- 2Changchun University of Chinese Medicine Affiliated Hospital
Abstract
Bone sialoprotein (BSP) is a non-collagenous extracellular matrix protein that participates in bone matrix mineralization and skeletal remodeling. However, its regulatory mechanisms and specific contributions to osteoporosis remain incompletely understood. This review summarizes the structural and functional characteristics of BSP, examines its roles in osteoblast-mediated bone formation, osteoclast-associated bone resorption, and remodeling coupling, and evaluates the evidence linking BSP to osteoporosis-associated skeletal abnormalities. BSP regulates matrix organization and mineral deposition through its interactions with collagen and hydroxyapatite, while its RGD motif mediates integrin-dependent cell–matrix signaling. Experimental studies indicate that BSP contributes to osteoblast-mediated matrix maturation and modulates osteoclast differentiation, adhesion, and resorptive activity. However, these effects are context-dependent and influenced by molecular modifications, cellular background, and the local microenvironment. Although human genetic and experimental studies have linked IBSP/BSP to postmenopausal or estrogen-deficiency-related skeletal phenotypes, direct BSP-specific evidence in glucocorticoid-induced, age-related, and diabetes-associated osteoporosis remains limited, and current evidence is insufficient to establish its causal contribution to osteoporotic bone loss. Evidence from genetic and intervention studies supports its functional involvement in skeletal remodeling, but the direct applicability of findings from non-osteoporotic models remains limited. Future investigations integrating disease-specific models, cell-targeted genetic manipulation, functional rescue experiments, and longitudinal assessments are needed to clarify the causal role of BSP and its potential clinical relevance. Collectively, BSP may serve as a context-dependent regulatory molecule linking extracellular matrix properties with bone cell responses, rather than a unidirectional regulator of bone formation or resorption.
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BibTeX
@article{meng2026bone,
title = {{Bone sialoprotein in bone remodeling: mechanisms of action, context dependence, and evidence related to osteoporosis}},
author = {Gang Meng and Ruijie Hou and Ping Dong and Hao Wu and Xueyuan Li and Kai Hu and Muren Huhe and Zixuan Du and Zhaoxin Zhong and Zhenxin Guo},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.2002399},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.2002399/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bone sialoprotein in bone remodeling: mechanisms of action, context dependence, and evidence related to osteoporosis
AU - Gang Meng
AU - Ruijie Hou
AU - Ping Dong
AU - Hao Wu
AU - Xueyuan Li
AU - Kai Hu
AU - Muren Huhe
AU - Zixuan Du
AU - Zhaoxin Zhong
AU - Zhenxin Guo
PY - 2026
DA - 2026/11/02
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.2002399
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.2002399/full
AB - Bone sialoprotein (BSP) is a non-collagenous extracellular matrix protein that participates in bone matrix mineralization and skeletal remodeling. However, its regulatory mechanisms and specific contributions to osteoporosis remain incompletely understood. This review summarizes the structural and functional characteristics of BSP, examines its roles in osteoblast-mediated bone formation, osteoclast-associated bone resorption, and remodeling coupling, and evaluates the evidence linking BSP to osteoporosis-associated skeletal abnormalities. BSP regulates matrix organization and mineral deposition through its interactions with collagen and hydroxyapatite, while its RGD motif mediates integrin-dependent cell–matrix signaling. Experimental studies indicate that BSP contributes to osteoblast-mediated matrix maturation and modulates osteoclast differentiation, adhesion, and resorptive activity. However, these effects are context-dependent and influenced by molecular modifications, cellular background, and the local microenvironment. Although human genetic and experimental studies have linked IBSP/BSP to postmenopausal or estrogen-deficiency-related skeletal phenotypes, direct BSP-specific evidence in glucocorticoid-induced, age-related, and diabetes-associated osteoporosis remains limited, and current evidence is insufficient to establish its causal contribution to osteoporotic bone loss. Evidence from genetic and intervention studies supports its functional involvement in skeletal remodeling, but the direct applicability of findings from non-osteoporotic models remains limited. Future investigations integrating disease-specific models, cell-targeted genetic manipulation, functional rescue experiments, and longitudinal assessments are needed to clarify the causal role of BSP and its potential clinical relevance. Collectively, BSP may serve as a context-dependent regulatory molecule linking extracellular matrix properties with bone cell responses, rather than a unidirectional regulator of bone formation or resorption.
SN - 1664-2392
ER -