Dataset Information

Molecular Basis for Periodontal Ligament Adaptation to In Vivo Loading.

ABSTRACT: A soft food diet leads to changes in the periodontal ligament (PDL). These changes, which have been recognized for more than a century, are ascribed to alterations in mechanical loading. While these adaptive responses have been well characterized, the molecular, cellular, and mechanical mechanisms underlying the changes have not. Here, we implicate Wnt signaling in the pathoetiology of PDL responses to underloading. We show that Wnt-responsive cells and their progeny in the PDL space exhibit a burst in proliferation in response to mastication. If an animal is fed a soft diet from the time of weaning, then this burst in Wnt-responsive cell proliferation is quelled; as a consequence, both the PDL and the surrounding alveolar bone undergo atrophy. Returning these animals to a hard food diet restores the Wnt signaling in PDL. These data provide, for the first time, a molecular mechanism underlying the adaptive response of the PDL to loading.

SUBMITTER: Zhang X

PROVIDER: S-EPMC6385351 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Molecular Basis for Periodontal Ligament Adaptation to In Vivo Loading.

Zhang X X Yuan X X Xu Q Q Arioka M M Van Brunt L A LA Shi Y Y Brunski J J Helms J A JA

Journal of dental research 20190105 3

A soft food diet leads to changes in the periodontal ligament (PDL). These changes, which have been recognized for more than a century, are ascribed to alterations in mechanical loading. While these adaptive responses have been well characterized, the molecular, cellular, and mechanical mechanisms underlying the changes have not. Here, we implicate Wnt signaling in the pathoetiology of PDL responses to underloading. We show that Wnt-responsive cells and their progeny in the PDL space exhibit a b ...[more]

PMID: 30612508

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Project description:The structural and functional integrity of bone-periodontal ligament (PDL)-cementum complex stems from the load-bearing attachment sites (entheses) between soft (PDL) and hard (bone, cementum) tissues. These attachment sites are responsible for the maintenance of a bone-PDL-cementum complex biomechanical function. The objective was to investigate changes in spatiotemporal expression of key biomolecules in developing and functionally active entheses.Multilabeling technique was performed on hemimandibles of 3 wk and 3 mo-old scleraxis-GFP transgenic mice for CD146, CD31, NG2, osterix and bone sialoprotein. Regions of dominant stretch within the PDL were evaluated by identifying directionality of collagen fibrils, PDL fibroblasts and PDL cell cytoskeleton.CD146+ cells adjacent to CD31+ vasculature were identified at PDL-bone enthesis. NG2+ cells were located at coronal bone-PDL and apical cementum-PDL entheses in the 3-wk-old group, but at 3 mo, NG2 was positive at the entheses of the apical region and alveolar crest. NG2 and osterix were colocalized at the osteoid and cementoid regions of the PDL-bone and PDL-cementum entheses. Bone sialoprotein was prominent at the apical region of 3-wk-old mice. The directionality of collagen fibers, fibroblasts and their cytoskeleton overlapped, except in the apical region of 3 wk.Colocalization of biomolecules at zones of the PDL adjacent to attachment sites may be essential for the formation of precementum and osteoid interfaces at a load-bearing bone-PDL-tooth fibrous joint. Biophysical cues resulting from development and function can regulate recruitment and differentiation of stem cells potentially from a vascular origin toward osteo- and cemento-blastic lineages at the PDL-bone and PDL-cementum entheses. Investigating the coupled effect of biophysical and biochemical stimuli leading to cell differentiation at the functional attachment sites is critical for developing regeneration strategies to enable functional reconstruction of the periodontal complex.

Project description:Background:The periodontal ligament cells (PDLCs) contain heterogeneous cell populations and possess stem-cell-like properties. PDLCs have attracted considerable attention as an option for periodontal regeneration. However, the osteogenic differentiation of PDLCs remains obscure owing to variable osteo-inductive methods and whether PDLCs could be directly used for periodontal regeneration without stem cell enrichment is uncertain. The aim of the present study was to clarify the osteogenic differentiation capacity of PDLCs and test PDLCs as an alternative to stem cells for periodontal regeneration. Methods:We tested the performance of human PDLCs in osteo-inductive culture and transplantation in vivo while taking human bone marrow derived mesenchymal stem cells (hMSCs) as positive control. Proliferation of PDLCs and hMSCs in osteo-inductive condition were examined by MTT assay and colony formation assay. The osteogenic differentiations of PDLCs and hMSCs were assessed by Alkaline phosphatase (ALP) activity measurement, von Kossa staining, Alizarin red S staining and quantitative RT-PCR of osteogenic marker gene including RUNX2, ALP, OCN, Col I, BSP, OPN. We transplanted osteo-inductive PDLCs and hMSCs with hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds to immunodeficient mice to explore their biological behaviors in vivo by histological staining and immunohistochemical evaluation. Results:After 14 days of osteo-induction, PDLCs exhibited significantly higher proliferation rate but lower colony-forming ability comparing with hMSCs. PDLCs demonstrated lower ALP activity and generated fewer mineralized nodules than hMSCs. PDLCs showed overall up-regulated expression of RUNX2, ALP, OCN, Col I, BSP, OPN after osteo-induction. Col I level of PDLCs in osteo-inductive group was significantly higher while RUNX2, ALP, OCN were lower than that of hMSCs. Massive fiber bundles were produced linking or circling the scaffold while the bone-like structures were limited in the PDLCs-loaded HA/TCP samples. The fiber bundles displayed strong positive Col I, but weak OCN and OPN staining. The in vivo results were consistent with the in vitro data, which confirmed strong collagen forming ability and considerable osteogenic potential of PDLCs. Conclusion:It is encouraging to find that PDLCs exhibit higher proliferation, stronger collagen fiber formation capacity, but lower osteogenic differentiation ability in comparison with hMSCs. This characteristic is essential for the successful periodontal reconstruction which is based on the synchronization of fiber formation and bone deposition. Moreover, PDLCs have advantages such as good accessibility, abundant source, vigorous proliferation and evident osteogenic differentiation capacity when triggered properly. They can independently form PDL-like structure in vivo without specific stem cell enrichment procedure. The application of PDLCs may offer a novel cytotherapeutic option for future clinical periodontal reconstruction.

Dataset Information

Molecular Basis for Periodontal Ligament Adaptation to In Vivo Loading.

Publications

Molecular Basis for Periodontal Ligament Adaptation to In Vivo Loading.

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