The periodontal ligament (PDL), which connects the teeth to the alveolar bone, is essential for periodontal tissue homeostasis. Although the significance of the PDL is recognized, molecular mechanisms underlying PDL function are not well known. We report that mohawk homeobox (Mkx), a tendon-specific transcription factor, regulates PDL homeostasis by preventing its degeneration. Mkx is expressed in the mouse PDL at the age of 10 weeks and expression remained at similar levels at 12 months. In Mkx mice, age-dependent expansion of the PDL at the maxillary first molar (M1) furcation area was observed. Transmission electron microscopy (TEM) revealed that Mkx mice presented collagen fibril degeneration in PDL with age, while the collagen fibril diameter gradually increased in Mkx mice. PDL cells lost their shape in Mkx mice, suggesting changes in PDL properties. Microarray and quantitative polymerase chain reaction (qPCR) analyses of Mkx PDL revealed an increase in osteogenic gene expression and no change in PDL- and inflammatory-related gene expression. Additionally, COL1A1 and COL1A2 were upregulated in Mkx-overexpressing human PDL fibroblasts, whereas osteogenic genes were downregulated. Our results indicate that Mkx prevents PDL degeneration by regulating osteogenesis.
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http://dx.doi.org/10.1242/dev.135798 | DOI Listing |
J Orthop Surg Res
December 2024
Department of Orthopedics, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, 315000, China.
Background: Tendinopathy is very common in clinical practice, which is highly prevalent in athletes, sports enthusiasts and other people involved in high-load weight-bearing activities. Common types of tendinopathy include rotator cuff injury, Achilles tendinitis, tennis elbow and so on. Macrophages (Macs) are key immune cells in the pathogenesis of tendinopathy.
View Article and Find Full Text PDFBone Rep
December 2024
Universite Claude Bernard Lyon 1, CNRS, UMR 5246, ICBMS, F-69622 Villeurbanne, France.
Biomechanical stimulation is proposed to occupy a central place in joint homeostasis, but the precise contribution of exercise remains elusive. We aimed to characterize in vivo the impact of mechanical stimulation on the cell-controlled regulation of ossification within the ankles of healthy mice undergoing mild physical activity. DBA/1 male mice were subjected to voluntary running exercise for two weeks, and compared to mice housed in standard conditions ( = 20 per group).
View Article and Find Full Text PDFCell Death Dis
June 2024
Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
The regeneration of the mammalian skeleton's craniofacial bones necessitates the action of intrinsic and extrinsic inductive factors from multiple cell types, which function hierarchically and temporally to control the differentiation of osteogenic progenitors. Single-cell transcriptomics of developing mouse calvarial suture recently identified a suture mesenchymal progenitor population with previously unappreciated tendon- or ligament-associated gene expression profile. Here, we developed a Mohawk homeobox (Mkx; R26R) reporter mouse and demonstrated that this reporter identifies an adult calvarial suture resident cell population that gives rise to calvarial osteoblasts and osteocytes during homeostatic conditions.
View Article and Find Full Text PDFJ Orthop Res
October 2024
Department of Orthopedic Surgery, National Defense Medical College, Saitama, Japan.
Traumatic heterotopic ossification is a condition in which extraskeletal bone formation occurs in soft tissues after injury. It most commonly occurs in patients who had major orthopedic surgery and in those with severe extremity injuries. The lesion causes local pain and can impair motor function of the affected limb, but there is currently no established prophylaxis or treatment for this condition.
View Article and Find Full Text PDFInt J Mol Sci
May 2024
School of Life Sciences, Arizona State University, 427 E Tyler Mall, Tempe, AZ 85287, USA.
Efficient repair of skeletal muscle relies upon the precise coordination of cells between the satellite cell niche and innate immune cells that are recruited to the site of injury. The expression of pro-inflammatory cytokines and chemokines such as TNFα, IFNγ, CXCL1, and CCL2, by muscle and tissue resident immune cells recruits neutrophils and M1 macrophages to the injury and activates satellite cells. These signal cascades lead to highly integrated temporal and spatial control of muscle repair.
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