image: Phosphorylation of ERK and p38 MAPK signaling pathways was markedly impaired in Bgn/Dcn double KO mice. Whole bone lysates extracted from the cortical bones of WT, Dcn HO, Bgn HO, and Bgn HO/Dcn HT mice were analyzed by western blot using antibodies against (a) phosphorylated ERK (p-ERK), total ERK, and β-actin, and (b) phosphorylated p38 MAPK (p-p38 MAPK), total MAPK, and β-actin. c ERK phosphorylation was determined by normalizing the intensity of p-ERK protein bands to total ERK. d Total ERK was determined by normalizing the intensity of ERK protein bands to β-actin. e p38 MAPK phosphorylation was quantified by normalizing the intensity of p-p38 MAPK protein bands to total p38 MAPK. n = 3 mice/group. f Total p38 MAPK was determined by normalizing the intensity of p38 MAPK protein bands to β-actin. g Schematic summary of the roles of Bgn and Dcn in water retention and the activation of ERK and p38 MAPK signaling pathways (modified from13,24). Dcn and Bgn are characterized by one or two chondroitin sulfate/dermatan sulfate chains attached to horseshoe-shaped core proteins, respectively. The GAG chains are highly negatively charged, which play a pivotal role in retaining bound water, thus conferring ductility and plasticity to bone. Bgn and Dcn have been reported to interact with various cytokines, growth factors, and cell surface receptors to form stable complexes, thereby activating downstream pathways that regulate bone homeostasis.13,26,27 Specifically, our data suggest that Bgn and Dcn are indispensable for the activation of ERK and p38 MAPK signaling pathways, which may explain the compensatory response observed between these two PGs. Figure created using BioRender (https://biorender.com/). Data are presented as mean ± SEM. One-way ANOVA with Tukey test was used for statistical analysis. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.000 1.
Credit: Bone Research
A recent study has uncovered the essential roles of two proteoglycans, biglycan and decorin, in maintaining bone mass, water retention, and bulk/in situ mechanical competence. Through the use of genetically modified mouse models, the research demonstrates that while biglycan plays a predominant role in preserving bone structure and toughness, decorin significantly contributes to the bone’s mechanical properties. These findings reveal how these proteins interact with water and other matrix components to regulate the mechanical behavior of bone. The results open new doors to understanding bone biology and could lead to the development of innovative treatments for bone-related diseases like osteoporosis.
Bone tissue is a complex structure, consisting of mineralized collagen fibers and a variety of non-collagenous proteins, including proteoglycans such as biglycan and decorin. These proteoglycans interact with water and other components in the extracellular matrix, playing a critical role in influencing the mechanical properties of bone. Despite their importance, the specific functions of biglycan and decorin in bone health have not been well understood. Given their potential impact on conditions like osteoporosis, there is a growing need for research to better comprehend the roles these proteoglycans play in maintaining bone integrity.
In a study (DOI: 10.1038/s41413-024-00380-2) published on January 2, 2025, in Bone Research, researchers from the University of Texas Health Science Center and the University of Texas at San Antonio examined the roles of biglycan and decorin in bone structure and function. Using genetically modified mouse models, including single and double knockout (KO) mice, the team investigated how the absence of these proteoglycans affects bone mass, water retention, bulk/in situ tissue properties, and cell signaling pathways.
This research, led by the University of Texas Health Science Center and the University of Texas at San Antonio, has provided significant insights into the critical roles of biglycan and decorin in bone health. The study found that biglycan deficiency led to a substantial decrease in trabecular bone mass and fracture toughness, while decorin deficiency, though less impactful on bone mass, still influenced bone's mechanical properties. Both proteoglycans were shown to be crucial for retaining bound water in the bone matrix, which is essential for maintaining bone toughness and flexibility. Advanced technologies such as low-field nuclear magnetic resonance and atomic force microscopy were employed to measure changes in bone structure and mechanical properties. The results indicated that biglycan and decorin activate the ERK and p38 MAPK signaling pathways, which are vital for bone remodeling and homeostasis. This study not only clarifies the distinct functions of these proteoglycans but also highlights their complementary effects in maintaining bone health, suggesting that targeting these pathways could provide new therapeutic avenues for preventing fractures and enhancing bone strength in patients with bone diseases.
Dr. Jean X. Jiang, one of the lead researchers, commented, “Our findings underscore the critical role of biglycan and decorin in bone structure and function. Understanding these mechanisms could pave the way for developing novel therapies to enhance bone strength and prevent fractures in patients with bone diseases.”
The implications of this study extend far beyond the laboratory. By revealing the roles of biglycan and decorin, scientists can now explore targeted interventions aimed at improving bone health. These findings may lead to the development of new treatments for osteoporosis and other bone disorders, potentially enhancing the quality of life for millions of individuals worldwide. Furthermore, the research offers valuable insights into the fundamental biology of bone, contributing to a deeper understanding of how bones maintain their strength and resilience over time.
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References
DOI
Original Source URL
https://doi.org/10.1038/s41413-024-00380-2
Funding information
This work was supported by the National Institutes of Health (NIH) Grants: RO1 AR076190 (to X.W and J.X.J) and Welch Foundation grant: AQ-1507 (to J.X.J.).
About Bone Research
Bone Research was founded in 2013. As a new English-language periodical, Bone Research focuses on basic and clinical aspects of bone biology, pathophysiology and regeneration, and supports the foremost discoveries resulting from basic investigations and clinical research related to bone. The aim of the Journal is to foster the worldwide dissemination of research in bone-related physiology, pathology, diseases and treatment.
Journal
Bone Research
Subject of Research
Not applicable
Article Title
Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness
Article Publication Date
2-Jan-2025
COI Statement
The authors declare that they have no competing interests.