Radiographic and clinical comparisons between loose-fit and press-fit stems in monopolar radial head arthroplasty for comminuted radial head fractures.

PURPOSE: Few clinical studies have compared the operative outcomes between loose- and press-fit stems in radial head arthroplasty (RHA). We aimed to evaluate the radiographic and clinical results of the two radial head implant concepts. METHODS: In this retrospective multicenter study, 32 patients (24 women and 8 men) with a mean age of 63.1 years who underwent RHA for comminuted radial head fractures were reviewed between 2005 and 2021. Seventeen patients underwent RHA with a loose-fit stem (L-group), whereas the remaining fifteen patients underwent RHA with a press-fit stem (P-group). The mean follow-up period was 40.1 ± 9.9 months, with the minimum follow-up duration of 12 months. The radiographic findings were evaluated for periprosthetic osteolysis; furthermore, clinical outcomes were analyzed to measure the range of motion of the elbow. The rate of reoperations and prosthesis removal were also reviewed. RESULTS: The general characteristics of the patients were similar in the two groups. The rate of periprosthetic osteolysis was 17.6% in the L-group, whereas it was 53.3% in the P-group. The mean elbow flexions were 128° and 133° in the L- and P-groups, respectively. The mean elbow extensions were -12° and -9° in the L- and P-groups, respectively. The rate of reoperation was 23.5% in the L-group and 15.2% in the P-group. One patient in the L-group had the prosthesis removed because of surgical site infection, whereas one patient in the P-group had the prosthesis removed owing to painful loosening. CONCLUSIONS: No significant differences in the clinical outcomes and reoperation rate were observed between the two radial head implant concepts in this study. However, osteolysis occurred more frequently in the P-group. Although patients with periprosthetic osteolysis are currently asymptomatic, they should be carefully followed up for the symptoms in the long term.

The transcription factor mohawk homeobox regulates homeostasis of the periodontal ligament.

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.

Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis.

Cell-based or pharmacological approaches for promoting tendon repair are currently not available because the molecular mechanisms of tendon development and healing are not well understood. Although analysis of knockout mice provides many critical insights, small animals such as mice have some limitations. In particular, precise physiological examination for mechanical load and the ability to obtain a sufficient number of primary tendon cells for molecular biology studies are challenging using mice. Here, we generated Mohawk (Mkx)(-/-) rats by using CRISPR/Cas9, which showed not only systemic hypoplasia of tendons similar to Mkx(-/-) mice, but also earlier heterotopic ossification of the Achilles tendon compared with Mkx(-/-) mice. Analysis of tendon-derived cells (TDCs) revealed that Mkx deficiency accelerated chondrogenic and osteogenic differentiation, whereas Mkx overexpression suppressed chondrogenic, osteogenic, and adipogenic differentiation. Furthermore, mechanical stretch stimulation of Mkx(-/-) TDCs led to chondrogenic differentiation, whereas the same stimulation in Mkx(+/+) TDCs led to formation of tenocytes. ChIP-seq of Mkx overexpressing TDCs revealed significant peaks in tenogenic-related genes, such as collagen type (Col)1a1 and Col3a1, and chondrogenic differentiation-related genes, such as SRY-box (Sox)5, Sox6, and Sox9 Our results demonstrate that Mkx has a dual role, including accelerating tendon differentiation and preventing chondrogenic/osteogenic differentiation. This molecular network of Mkx provides a basis for tendon physiology and tissue engineering.

[Analysis of Musculoskeletal Systems and Their Diseases. The research for musculoskeletal disease using genome editing technology].

Genome editing is a genetic technology by which any DNA sequence is inserted, replaced or deleted. Genome editing has been making rapid progress recently, with the development of new techniques such as ZFN, TALEN and CRISPR/Cas9. Genome editing can be applied to various fields ranging from the production of knock out animals to gene therapy. This section summarizes these new genome editing technologies and its applications.

Evaluation of Ulnar Setting of Volar Locking Plates for Distal Radius Fractures Using Modified Skyline View.

Purpose: Volar lunate facet fragments in distal radius fractures are located at the center of the load in the wrist joint and, therefore, should be properly supported by the distal ulnar setting of volar locking plates to obtain better postoperative outcomes. This study evaluated the usefulness of the modified skyline view (MSV) in intraoperative fluoroscopy for the ulnar setting of volar locking plates by comparing it with that of the anteroposterior view (APV). Methods: Sixty-five patients with distal radius fractures who underwent open reduction and plate fixation as well as follow-up intraoperative fluoroscopy and postoperative computed tomography (CT) at our institution between April 2019 and March 2022 were included. The distance between the ulnar edge of the plate and the distal radius (d-value) was measured retrospectively using intraoperative fluoroscopy (distance measured from MSV and distance measured from APV) or postoperative CT (distance measured using postoperative CT). The distance measured from MSV and that measured from APV were compared with those measured using CT as the true values. Each measurement was performed twice by 2 examiners at an interval of 1 month. The comparison scores were evaluated using the intraclass correlation coefficient. Results: The distance measured from MSV showed a difference of 0.6 ± 0.5 mm from that measured using CT, which was significantly smaller than that measured from APV (1.2 ± 0.9 mm; P < .001). Neither postoperative volar subluxation nor dislocation of bone fragments was found during the study period. Both intraclass correlation coefficient (1,1) and intraclass correlation coefficient (2,1) reliabilities were substantial to almost perfect. Conclusions: Modified skyline view is an effective and versatile imaging method for estimating the ulnar setting of volar locking plates; it provides measurements more similar to those provided by postoperative CT compared with APV. The use of MSV may reduce postoperative complications, such as volar subluxation and dislocation of bone fragments, especially in cases with volar lunate facet fragments in which the ulnar setting of the plate is significant. Type of study/level of evidence: Diagnostic III.

Identification of a Biallelic Missense Variant in Gasdermin D (c.823G > C, p.Asp275His) in a Patient of Atypical Gorham-Stout Disease in a Consanguineous Family.

Gorham-Stout disease (GSD), also called vanishing bone disease, is a rare osteolytic disease, frequently associated with lymphangiomatous tissue proliferation. The causative genetic background has not been noted except for a case with a somatic mutation in KRAS. However, in the present study, we encountered a case of GSD from a consanguineous family member. Whole-exome sequencing (WES) analysis focusing on rare recessive variants with zero homozygotes in population databases identified a homozygous missense variant (c.823G > C, p.Asp275His) in gasdermin D (GSDMD) in the patient and heterozygous in his unaffected brother. Because this variant affects the Asp275 residue that is involved in proteolytic cleavage by caspase-11 (as well as -4 and -5) to generate an activating p30 fragment required for pyroptotic cell death and proinflammation, we confirmed the absence of this cleavage product in peripheral monocytic fractions from the patient. A recent study indicated that a shorter p20 fragment, generated by further cleavage at Asp88, has a cell-autonomous function to suppress the maturation of osteoclasts to resorb bone matrix. Thus, the present study suggests for the first time the existence of hereditary GSD cases or novel GSD-like diseases caused by GSDMD deficiency. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Reliability and validity of measuring temporal muscle thickness as the evaluation of sarcopenia risk and the relationship with functional outcome in older patients with acute stroke.

BACKGROUND: Pre-stroke sarcopenia associated with poor functional outcomes. However, diagnosis of pre-stroke sarcopenia is often difficult in patients with acute stroke. Thus, we investigated the reliability and validity of measuring temporal muscle thickness (TMT) as an indicator of sarcopenia risk and its relationship with functional outcome in older patients with acute stroke. METHODS: We conducted a cross-sectional and longitudinal study of the patients with acute elderly stroke in a single neurosurgical hospital. We measured TMT manually using brain computed tomography (CT) by two examiners. Sarcopenia risk, malnutrition risk, inflammation, comorbidities, and modified Rankin Scale (mRS) scores at 3 months after stroke were additionally assessed. Inter-rater reliability of TMT was determined by calculating the intra-class correlation coefficient ([ICC] 2,1). Multiple linear regression analyses was used to determine whether sarcopenia risk was independently associated with TMT, and logistic regression was used to evaluate the relationship between TMT and poor functional outcome (mRS > 3). RESULTS: A total 289 acute elderly stroke patients (163 men and 126 women; mean age: 76 years) were enrolled in this study. Regarding the reproducibility of TMT, good reliability was found; ICC2,1 = 0.759 (95 % confidence interval = 0.705-0.804). Multiple linear regression analyses for TMT after adjusting for potential confounders showed that sarcopenia risk was independently associated with TMT in older patients with acute stroke (ß = -0.138, p = 0.02). After adjusting for variables, disease severity and comorbidities were the only independent predictors for poor functional outcome, but not TMT. CONCLUSIONS: TMT measurement using brain CT is a reliable and variable method to evaluate sarcopenia risk, but is not related to functional outcome in older patients with acute stroke.

Mallet Finger Fracture through Enchondroma of the Distal Phalanx.

A 46-year-old man injured his ring finger and developed a mallet deformity. Radiographs showed a mallet finger fracture through an osteolytic lesion of the distal phalanx. Magnetic resonance imaging showed low intensity on T1-weighted imaging and high intensity on T2-weighted imaging, which suggested the clinical diagnosis of enchondroma. The bone tumor was excised, and osteosynthesis was performed using Ishiguro's extension block pinning, and a flexion block pin was added to prevent flexor tendon avulsion fracture through the enchondroma, followed by an autologous iliac cancellous bone graft. One year after surgery, the patient had no pain or extension lag of the affected ring finger, and his quickDASH score was 0 points. Radiographs showed no recurrence and minimal arthritic change of the distal interphalangeal joint. One-stage treatment of a mallet finger fracture through an enchondroma using Ishiguro's method was effective.

Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon.

Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx(-/-) mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration.

Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.

The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx(-/-) mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration.