Raman spectroscopic fingerprinting uncovers a multi-scale structural-mechanical-transcriptomic coupling landscape in
Jinyang Wang1,2, Yongxi Lu1,2,3, Xinwei Zhou1,2
1Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
Background:
Osteoporosis is a systemic skeletal disorder characterized by reduced bone strength and increased fracture risk. Conventional evaluation relies mainly on bone mineral density and microarchitecture, but these measures do not fully capture the tissue-level material properties that contribute to fragility. Here, we integrated Raman-derived compositional information with microarchitectural, local mechanical, and single-cell transcriptomic data to map a multi-scale coupling landscape and identify a conserved compositional fingerprint of osteoporotic trabecular bone.
Methods:
Trabecular bone alterations were profiled by Raman spectroscopy in murine models of natural aging and ovariectomy (OVX)-induced osteoporosis. A linear support vector machine (LSVM) classifier was trained for automated phenotyping of Raman spectra. Raman-defined spectral features were then integrated with micro-CT-based microarchitectural measurements, nanoindentation-derived local mechanical properties, and single-cell RNA sequencing (scRNA-seq) of bone marrow mesenchymal stem cells (BMMSCs) to contextualize compositional changes across structure, mechanics, and remodeling programs.
Results:
We identified a conserved osteoporotic Raman fingerprint characterized by reduced phosphate and collagen signals and increased lipid-associated bands. These compositional signatures were strongly associated with micro-CT-defined structural deterioration and nanoindentation-derived local mechanical alterations, specifically reduced hardness and increased elastic modulus. Furthermore, scRNA-seq revealed shifts in BMMSC transcriptomic programs related to mineral, extracellular matrix, and lipid metabolism that paralleled the Raman-defined changes. The OVX model further confirmed the etiological robustness of this Raman fingerprint in capturing multi-scale alterations in bone quality.
Conclusions:
Raman-based compositional fingerprinting provides a multidimensional readout that can be integrated with structural imaging, mechanical testing, and transcriptomic profiling. This cross-scale framework refines osteoporosis evaluation, supports the development of advanced diagnostic strategies, and offers mechanistic insight into bone fragility beyond conventional structural metrics.
Related Concept Videos
02:24Ribosome Profiling
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
01:10X-ray Diffraction of Biological Samples
According to Bragg's law, when X-rays strike the sample positioned on a stage, the rays are scattered by the electron clouds around the sample atoms. The X-ray diffraction or scattering is caused by constructive interference of the X-ray waves that reflect off the internal crystal...
01:31Osteoclasts in Bone Remodeling
01:31Bone Remodeling and Repair
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...