Ryo Nakamichi

The Scripps Research Institute | scripps · Department of Molecular and Experimental Medicine

How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1 was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1 , a mouse gain-of-function variant, and...

Tendons play an important role in the maintenance of motor function by connecting muscles and bones and transmitting forces. Particularly, the role of mechanical stress has primarily focused on the key mechanism of tendon homeostasis, with much research on this topic. With the recent development of molecular biological techniques, the mechanisms of...

Background The purpose of this study was to examine two techniques for Carpal Tunnel Syndrome, mini-Open Carpal Tunnel Release (mini-OCTR) and Endoscopic Carpal Tunnel Release (ECTR), to compare their therapeutic efficacy. Methods Sixteen patients who underwent mini-OCTR in palmar incision and 17 patients who underwent ECTR in the wrist crease inc...

Background: It is not clear whether rehabilitation after surgery for trigger finger is effective. The aim of this study was to reveal its effectiveness for trigger finger. Methods: This study was a randomized, controlled trial that included patients who underwent operations for trigger fingers. The patients in the rehabilitation group had postopera...

Rupture of the extensor pollicis longus (EPL) tendon is a known complication after undisplaced distal radius fracture (DRF). However, no report has revealed the relationship between EPL tendon rupture and the fracture pattern. Thus, this study aimed to investigate the characteristics of fractures at risk of EPL tendon rupture using fracture line ma...

When focusing on quick movements in the analysis of animal behavior, a high-speed camera can be used as a powerful tool. There are many options for high-speed cameras to record movement. In recent years, the quality and sophistication of videos captured on cell phones have evolved so much that the iPhone's slow-motion video system can function as a...

The periodontal ligament (PDL) comprises a fibrous tissue that connects teeth to alveolar bone and is essential for periodontal function. The transcription factor mohawk homeobox (Mkx) is expressed in the PDL where it plays an important role in the development and maintenance of the PDL. However, the precise and critical functions of Mkx in the cel...

Tendons and ligaments are essential connective tissues that connect the muscle and bone. Their recovery from injuries is known to be poor, highlighting the crucial need for an effective therapy. A few reports have described the development of artificial ligaments with sufficient strength from human cells. In this study, we successfully generated a...

Tendons and ligaments are jointed to bones via an enthesis that is essential to the proper function of the muscular and skeletal structures. The aim of the study is to investigate the effect of mechanical stress on the enthesis. We used ex vivo models in organ cultures of rat Achilles tendons with calcaneus including the enthesis. The organ was att...

Osteoarthritis (OA), the most common aging-related joint disease, is caused by an imbalance between extracellular matrix synthesis and degradation. Here, we discover that both strands of microRNA-455 (miR-455), -5p and -3p, are up-regulated by Sox9, an essential transcription factor for cartilage differentiation and function. Both miR-455-5p and -3...

IntroductionThe periodontal ligament (PDL) plays an important role in orthodontic tooth movement; however, the underlying molecular mechanism remains unclear. We have previously reported that the Mohawk homeobox (Mkx), a tendon-specific transcription factor, is expressed in the PDL and regulates its homeostasis.Materials and methodsIn the present s...

MicroRNAs (miRNAs) are a class of noncoding small RNAs, which play a critical role in various biological processes including musculoskeletal formation and arthritis pathogenesis via regulating target gene expressions, raising the potentially substantial effects on gene expression networks. Over 2000 miRNAs are encoded in the human genome and a sing...

Tendons transmit power from muscles to bones, and ligaments maintain the stability of joints, thus producing smooth and flexible movements of articular joints. However, tendons have poor self-healing ability upon damage due to injuries, diseases, or aging. To maintain homeostasis or promote regeneration of the tendon/ligament, it is critical to und...

Tendons and ligaments are pivotal connective tissues that tightly connect muscle and bone. In this study, we developed a novel approach to generate tendon/ligament-like tissues with a hierarchical structure, by introducing the tendon/ligament-specific transcription factor Mohawk (MKX) into the mesenchymal stem cell (MSC) line C3H10T1/2 cells, and b...

Endochondral ossification is a critical event in bone formation, particularly in long shaft bones. Many cellular differentiation processes work in concert to facilitate the generation of cartilage primordium to formation of trabecular structures, all of which occur within the growth plate. Previous studies have revealed that the growth plate is tig...

Abstract Damage to the intervertebral discs (IVDs) occurs due to aging or excessive mechanical stress, causing a series of IVD‐related degenerative diseases, such as spinal disc herniation and spondylosis. These IVD‐related diseases are difficult to cure, partially because the regeneration ability of IVDs is not sufficient. As a novel strategy for...

The WW domain-containing protein 2 (Wwp2) gene, the host gene of miR-140, codes for the Wwp2 protein, which is an HECT-type E3 ubiquitin ligases abundantly expressed in articular cartilage. However, its function remains unclear. Here, we show that mice lacking Wwp2 and mice in which the Wwp2 E3 enzyme is inactivated (Wwp2-C838A) exhibit aggravated...

Tendons and ligaments play essential roles in connecting muscle and bone and stabilizing the connections between bones. The damage to tendons and ligaments caused by aging, injury, and arthritis induces the dysfunction of the musculoskeletal system and reduces the quality of life. Current therapy for damaged tendons and ligaments depends on self-re...

Ligaments of joint have an essential role of proper mobilization and stabilization between bone and bone. Damage to ligaments caused by ageing, injury, and arthritis induce a disability of musculoskeletal system and has a problem to reduce our quality of life. To aim for the regeneration of ligaments, we have researched from the point of view of th...

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 b...

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 t...

Supplementary Figures 1-12 and Supplementary Tables 1-3.

Significance Molecular mechanisms of tendon development and homeostasis are not well understood. Generation and analysis of Mkx −/− rats revealed new functions of Mohawk (Mkx) in mediating cellular responses to mechanical stress. An Mkx-ChIP assay in rat tendon-derived cells with Mkx expression suggested that this factor may associate with both ten...

Mechanoforces experienced by an organ is 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...