# The role of collagen cross-links in craniofacial bone quality and healing

> **NIH NIH F30** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $51,320

## Abstract

Project Summary Abstract:
Bone is continually remodeled and must maintain homeostasis of both the collagen and mineral components.
Collagen is the primary matrix protein found in bone; it provides the structural organization and is a
determinant of whole bone mechanical properties. Collagen is post-translationally modified by the lysyl oxidase
(LOX) enzyme family to produce a distinct profile of mature and immature cross-links. The composition of
cross-links is thought to alter the collagen fibril diameter and D-spacing, and altered fibril geometry may lead to
altered mineralization. In experimental models of perturbed collagen cross-links, the mechanical strength and
toughness directly correlate to the cross-link profile. Therefore, it is possible that compositional changes are
contributing to the altered structure and function in patients suffering from a variety of systemic conditions that
also exhibit reduced bone quality. The mechanisms controlling collagen cross-linking and mineralization in
homeostasis and healing are understudied in the axial skeleton and craniofacial bones. Collagen content and
relative cross-link maturity differ between the axial and craniofacial bones, and therefore may respond
differently to altered LOX activity. My preliminary data suggests that altered collagen-cross-link profiles may be
associated with an increase in the relative mineralization in the axial skeleton, but a decrease in the
craniofacial bone. My central hypothesis is that collagen cross-linking dictates mineralization by
controlling fibril diameter and collagen D-spacing and that inhibition of cross-linking compromises
bone quality and healing in osseous wound sites.
Two aims are proposed: 1) Define the role of collagen cross-links in craniofacial and axial bone mineralization,
i2) Determine the effect of impaired collagen cross-links on craniofacial bone quality during healing after molar
extraction. These studies will be accomplished using an established mouse model, where LOX-family enzymes
are inhibited by treatment with a pharmacological agent, beta-aminoproprionitrile (BAPN). This model reduces
the amount and alters the profile of cross-links in a dose dependent fashion. I will determine the fibril diameter
and D-spacing via atomic force microscopy, mineral and collagen changes via Raman spectroscopy, and
compare the response of craniofacial bone to axial bone. A molar extraction model will then be used to
determine the effect of partial LOX-family enzyme inhibition on healing in craniofacial bone. Histology and
histomorphometry will be used to determine the overarching effects on osteoblasts and osteoclasts. The
outcomes of the proposed experiments will gain insight into the role of collagen cross-links in mineral
composition, mechanical properties, and healing processes of axial and craniofacial bone for application in a
variety of systemic conditions. Collagen cross-links are relatively easily manipulated via the LOX-family
enzymes and there...

## Key facts

- **NIH application ID:** 9899733
- **Project number:** 5F30DE028167-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Genevieve Elizabeth Romanowicz
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $51,320
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899733

## Citation

> US National Institutes of Health, RePORTER application 9899733, The role of collagen cross-links in craniofacial bone quality and healing (5F30DE028167-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9899733. Licensed CC0.

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