Dataset Information

Systemic Lipid Metabolism Dysregulation as a Possible Driving Force of Fracture Nonunions? A Concomitant Proteomic and Metabolomic Pilot Study

ABSTRACT: In this study, we aimed to examine the differences in molecular profiles between nonunions and fractures that heal without significant complications. We compared blood samples in two groups of patients with similar characteristics but different outcomes in bone healing using plasma proteomics and plasma metabolomics in order to detect crucial proteins, metabolites as well as underlying biological processes that might be responsible for impairments in bone healing.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Bone Disease

SUBMITTER: Ruđer Novak

LAB HEAD: Lovorka Grgurevic

PROVIDER: PXD054887 | Pride | 2025-05-07

REPOSITORIES: Pride

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			Action	DRS
	20240221_MEF_pseudoartroza_38_01.raw	Raw
	20240221_MEF_pseudoartroza_38_02.raw	Raw
	20240221_MEF_pseudoartroza_40_01.raw	Raw
	20240221_MEF_pseudoartroza_40_02.raw	Raw
	20240221_MEF_pseudoartroza_42_01.raw	Raw

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Systemic Lipid Metabolism Dysregulation as a Possible Driving Force of Fracture Non-Unions?

Grgurević Lovorka L Novak Ruđer R Jambrošić Lucija L Močibob Marko M Jaganjac Morana M Halasz Mirna M Salai Grgur G Hrkač Stela S Milošević Milan M Vlahović Tomislav T Romić Jeronim J Matičić Dražen D Vidović Dinko D

Bioengineering (Basel, Switzerland) 20241111 11

<h4>Introduction</h4>Non-unions are fractures that do not heal properly, resulting in a false joint formation at the fracture site. This condition leads to major health issues and imposes a burden on national healthcare systems. The etiology of non-unions is still not fully understood; therefore, we aimed to identify potential systemic factors that may contribute to their formation.<h4>Materials and methods</h4>We conducted a cross-sectional concomitant proteomic and metabolomic pilot study of b ...[more]

PMID: 39593795

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Project description:Bone fractures, the most common musculoskeletal injuries, heal through three main phases: inflammatory, repair, and remodeling. Around 10% of fracture patients suffer from impaired healing that requires surgical intervention, a huge burden on the healthcare system. The rate of impaired healing increases with metabolic diseases such as obesity-associated hyperglycemia/type 2 diabetes (T2D), an increasing concern given the growing incidence of obesity/T2D. Immune cells play pivotal roles in fracture healing, and obesity/T2D is associated with defective immune-cell functions. However, there is a gap in knowledge regarding the stoichiometry of immune cells that populate the callus and how that population changes during different phases of healing. Here, we used complementary global and single-cell techniques to characterize the repertoire of immune cells in the fracture callus and to identify populations specifically enriched in the fracture callus relative to the unfractured bone or bone marrow. Our analyses identified two clear waves of immune-cell infiltration into the callus: the first wave occurs during the early inflammatory phase of fracture healing, while the second takes place during the late repair/early remodeling phase. Innate immune cells were activated during the early inflammatory phase, but in later phases they returned to homeostatic numbers and activation levels. Of the innate immune cells, distinct subsets of activated dendritic cells were particularly enriched in the inflammatory healing hematoma. In contrast to innate cells, lymphocytes, including B and T cells, were enriched and activated in the callus primarily during the late repair phase. The Diet-Induced Obesity (DIO) mouse, an established model of obesity-associated hyperglycemia and insulin resistance, suffers from multiple healing defects. Our data demonstrate that DIO mice exhibit dysregulated innate immune responses during the inflammatory phase, and defects in all lymphocyte compartments during the late repair phase. Taken together, our data characterize, for the first time, immune populations that are enriched/activated in the callus during two distinct phases of fracture healing and identify defects in the healing-associated immune response in DIO mice, which will facilitate future development of immunomodulatory therapeutics for impaired fracture healing.