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Medicina (Kaunas, Lithuania) Jun 2023Medial meniscus posterior root tears (MMRTs), defined as tears or avulsions that occur within 1 cm of the tibial attachment of the medial meniscus posterior root, lead... (Review)
Review
Medial meniscus posterior root tears (MMRTs), defined as tears or avulsions that occur within 1 cm of the tibial attachment of the medial meniscus posterior root, lead to biomechanically detrimental knee conditions by creating a functionally meniscal-deficient status. Given their biomechanical significance, MMRTs have recently been gaining increasing interest. Accordingly, numerous studies have been conducted on the anatomy, biomechanics, clinical features, diagnosis, and treatment of MMRTs, and extensive knowledge has been accumulated. Although a consensus has not yet been reached on several issues, such as surgical indications, surgical techniques, and rehabilitation protocols, this article aimed to comprehensively review the current knowledge on MMRTs and to introduce the author's treatment strategies.
Topics: Humans; Menisci, Tibial; Knee Joint; Tibia; Rupture
PubMed: 37511993
DOI: 10.3390/medicina59071181 -
Clinics in Orthopedic Surgery Oct 2023There is no consensus established on postoperative rehabilitation after medial meniscus posterior root tear (MMPRT) repair, including when and how physicians can apply...
BACKGROUND
There is no consensus established on postoperative rehabilitation after medial meniscus posterior root tear (MMPRT) repair, including when and how physicians can apply range of motion (ROM) exercise, weight-bearing (WB), brace use, and return to sports (RTS). The purpose of this study was to systematically review the literature on postoperative rehabilitation characteristics of MMPRT repair regarding ROM, WB, brace use, and RTS.
METHODS
A literature search was performed using the Medline/PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. The inclusion criteria were English language, human clinical studies, and studies describing rehabilitation protocols after MMPRT repair such as ROM, WB, brace use, and RTS. Abstracts, case reports, cohort studies, controlled laboratory studies, human cadaveric or animal studies, systematic reviews, and meta-analyses were excluded.
RESULTS
Thirteen studies were included. Of the 12 ROM studies, ROM was started immediately within 1 or 2 days after operation in 6 studies and after 2 to 3 weeks of knee immobilization in the rest. Of the 13 WB studies, partial weight-bearing was initiated 1 to 4 weeks after operation in 8 studies and 6 weeks in the rest. Of the 9 brace studies, patients were immobilized by a splint for 2 weeks in 3 studies, and in the rest, a brace with full extension was applied for 3 to 6 weeks after several days of splint application. Of the 7 RTS studies, RTS was allowed at 6 months in 6 studies and 5 to 7 months in 1 study.
CONCLUSIONS
This systematic review revealed conservative rehabilitation protocols were more widely adapted as ROM and WB were restricted at certain degrees during postoperative periods in most protocols analyzed. However, it is impossible to identify a consensus on rehabilitation protocols as the protocols analyzed in this review were distinct each other and heterogeneous. In the future, a well-designed comparative study among different rehabilitation protocols is essential to establish a consensus.
Topics: Humans; Menisci, Tibial; Return to Sport; Rupture; Arthroplasty, Replacement, Knee; Weight-Bearing
PubMed: 37811518
DOI: 10.4055/cios21231 -
Annals of the Rheumatic Diseases Sep 2023The activator protein-1 (AP-1) transcription factor component c-Fos regulates chondrocyte proliferation and differentiation, but its involvement in osteoarthritis (OA)...
OBJECTIVES
The activator protein-1 (AP-1) transcription factor component c-Fos regulates chondrocyte proliferation and differentiation, but its involvement in osteoarthritis (OA) has not been functionally assessed.
METHODS
c-Fos expression was evaluated by immunohistochemistry on articular cartilage sections from patients with OA and mice subjected to the destabilisation of the medial meniscus (DMM) model of OA. Cartilage-specific c-Fos knockout (c-Fos) mice were generated by crossing to mice. Articular cartilage was evaluated by histology, immunohistochemistry, RNA sequencing (RNA-seq), quantitative reverse transcription PCR (qRT-PCR) and metabolic enzyme assays. The effect of dichloroacetic acid (DCA), an inhibitor of pyruvate dehydrogenase kinase (Pdk), was assessed in c-Fos mice subjected to DMM.
RESULTS
FOS-positive chondrocytes were increased in human and murine OA cartilage during disease progression. Compared with c-Fos mice, c-Fos mice exhibited exacerbated DMM-induced cartilage destruction. Chondrocytes lacking c-Fos proliferate less, have shorter collagen fibres and reduced cartilage matrix. Comparative RNA-seq revealed a prominent anaerobic glycolysis gene expression signature. Consistently decreased pyruvate dehydrogenase (Pdh) and elevated lactate dehydrogenase (Ldh) enzymatic activities were measured , which are likely due to higher expression of hypoxia-inducible factor-1α, , and Pdk1 in chondrocytes. treatment of c-Fos mice with DCA restored Pdh/Ldh activity, chondrocyte proliferation, collagen biosynthesis and decreased cartilage damage after DMM, thereby reverting the deleterious effects of c-Fos inactivation.
CONCLUSIONS
c-Fos modulates cellular bioenergetics in chondrocytes by balancing pyruvate flux between anaerobic glycolysis and the tricarboxylic acid cycle in response to OA signals. We identify a novel metabolic adaptation of chondrocytes controlled by c-Fos-containing AP-1 dimers that could be therapeutically relevant.
Topics: Animals; Humans; Mice; Cartilage, Articular; Chondrocytes; Collagen; Disease Models, Animal; Osteoarthritis; Transcription Factor AP-1; Proto-Oncogene Proteins c-fos
PubMed: 37344157
DOI: 10.1136/ard-2023-224002 -
Annals of the Rheumatic Diseases Nov 2023Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in...
OBJECTIVES
Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of deficiency on the development of post-traumatic and age-associated OA in mice.
METHODS
Male cartilage-specific -deficient mice and intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting.
RESULTS
deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that depletion significantly repressed cartilage extracellular matrix (eg, ) and anabolic growth factor (eg, insulin-like growth factor-1 ()) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced activation promoted IGF-1 signalling by increasing Akt phosphorylation.
CONCLUSIONS
SIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA.
Topics: Male; Animals; Mice; Humans; Aged; Insulin-Like Growth Factor I; Osteophyte; Proto-Oncogene Proteins c-akt; Osteoarthritis; Chondrocytes; Cartilage, Articular; RNA; Sirtuins; Disease Models, Animal
PubMed: 37550003
DOI: 10.1136/ard-2023-224385