Regulation of energy metabolism in the growth plate and osteoarthritic chondrocytes

Abstract

Osteoarthritis (OA) is a chronic disorder associated mainly with pain, limited range of motion, stiffness, low-grade systemic inflammation, and articular cartilage destruction. Recent studies have demonstrated the involvement of chondrocyte differentiation (hypertrophy) as one of the mechanisms in cartilage degradation in OA. This implicates the involvement of principal changes in the regulation of cellular function associated with profound alterations in chondrocyte energy metabolism in the course of cartilage resorption. Therefore, this review describes the major energy-generating pathways and their regulatory molecules used by the growth plate chondrocytes during endochondral ossification and by articular chondrocytes in OA. These regulatory molecules facilitate either the glycolytic pathway of energy generation, which controls cell proliferation, or mitochondrial oxidative phosphorylation promoted by AMPK and sirtuins and responsible for tissue regeneration. Consideration of the disturbances in energy metabolic pathways associated with OA might provide an approach to disclose the primary causes of the disease's development and progression. Medline/PubMed was searched for publications in English using key words: osteoarthritis, epiphyseal growth plate, articular cartilage, glycolysis, oxidative phosphorylation, and regulation of energy metabolism.

MFN2 contributes to metabolic disorders and inflammation in the aging of rat chondrocytes and osteoarthritis

“…Meanwhile, an increase in oxidative phosphorylation was also be confirmed during aging to maintain ATP production. Similar phenomenon also occurs in hypertrophic chondrocytes, that hypertrophic chondrocytes rely more on mitochondrial respiration specifically in hypertrophic zone of the growth plate, as well as in OA cartilage 25,26 . Further, no significant differences in cellular senescence related changes were found, as we demonstrated that mitochondrial dysfunction contributed to metabolic disorders above all, it would not be unreasonable to assume that age-related mitochondrial dysfunction was prior to cellular senescence and might contribute to normal aging as well as OA 27,28 .…”

“…Chondrocytes, which rely on glycolysis to generate ATP for cellular energy 23 , may increase oxygen consumption as a compensatory way to maintain ATP production through the MRC when glycolysis is inhibited for any reason 24,25 . Energy metabolic homeostasis between glycolysis and oxidative phosphorylation in chondrocytes is critical for cellular survival and for maintaining extracellular matrix production 26 .…”

Inner histopathologic changes and disproportionate zone volumes in foetal growth plates following gestational hypoglycaemia in rats

“…In addition to a potential primary role of hypoxia in the development of the histopathologic growth plate changes, hypoglycaemia may also play an important role. The growth plate is a highly metabolic tissue, relying on anaerobic glycolysis 37 , and glucose serves as an essential source of energy 38 . Consequently, central chondrocytes may die due to glucose insufficiency and impaired glycolysis decreasing the energy supply.…”

Upcoming value of gene expression analysis in rheumatology

“…В связи с этим терапия должна приводить к общей нормализации метаболизма клеток всего организма [143]. Экспрессия генов является наиболее ранним ответом организма на изменения внешней и внутренней среды клетки задолго до изменения экспрессии соответствующих белков на тканевом и организменном уровнях [13] и поэтому может быть использована для экспресс-оценки состояния больного РЗ. Более того, изменения, происходящие в тканях и крови больных РА взаимосвязаны, поскольку показано, что в клетках крови больных РА повышена экспрессия генов, регулирующих морфогенез кости и хряща, по сравнению со здоровыми лицами [144] и отмечена корреляция экспрессии генов в крови и повреждённых тканях больных РА [145][146][147][148].…”

“…Напротив, анализ экспрессии генов в мононуклеарных клетках периферической крови может быть более адекватным подходом для идентификации биомаркеров для персонифицированной терапии вследствие системной природы РЗ [1]. Кроме того, поскольку экспрессия генов является наиболее ранним маркером изменений организма в ответ на заболевание или терапию [13], идентификация генов, контролирующих процессы развития заболевания и его терапии, может служить прогностическим инструментом в клинической практике.…”