Prospects of circadian clock in joint cartilage development

Song, Xiaopeng; Hu, Hailong; Zhao, Mingchao; Ma, Tianwen; Li, Gao

doi:10.1096/fj.202001597r

Cited by 3 publications

(5 citation statements)

References 205 publications

(312 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The circadian clock has been shown to play a key regulatory role in various tissues and organs, including the musculoskeletal system, and more specifically cartilage 15,47 . Our results, for the first time, suggest that entraining chondroprogenitor clocks during chondrogenesis by uniaxial cyclic mechanical load offers a novel and insightful way in which these cells can be primed to produce more abundant cartilage ECM.…”

Section: Discussionmentioning

confidence: 62%

“…The circadian clock has been shown to play a key regulatory role in various tissues and organs, including the musculoskeletal system, and more specifically cartilage. 15,47 Our results, for the first time, suggest that entraining chondroprogenitor clocks during chondrogenesis by uniaxial cyclic mechanical load offers a novel and insightful way in which these cells can be primed to produce more abundant cartilage ECM. Mechanical entrainment represents a noninvasive means by which the quality and quantity of tissue-engineered cartilage could be augmented through the control of the circadian clock in the critical period of chondrogenesis, avoiding the need for additional exogenous chemical or thermal stimuli.…”

Section: Discussionmentioning

confidence: 77%

See 1 more Smart Citation

Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock

Vágó

Katona

Takács

et al. 2022

Journal of Pineal Research

View full text Add to dashboard Cite

The biomechanical environment plays a key role in regulating cartilage formation, but the current understanding of mechanotransduction pathways in chondrogenic cells is incomplete. Among the combination of external factors that control chondrogenesis are temporal cues that are governed by the cell-autonomous circadian clock. However, mechanical stimulation has not yet directly been proven to modulate chondrogenesis via entraining the circadian clock in chondroprogenitor cells. The purpose of this study was to establish whether mechanical stimuli entrain the core clock in chondrogenic cells, and whether augmented chondrogenesis caused by mechanical loading was at least partially mediated by the synchronised, rhythmic expression of the core circadian clock genes, chondrogenic transcription factors, and cartilage matrix constituents at both transcript and protein levels. We report here, for the first time, that cyclic uniaxial mechanical load applied for 1 h for a period of 6 days entrains the molecular clockwork in chondroprogenitor cells during chondrogenesis in limb bud-derived micromass cultures. In addition to the several core clock genes and proteins, the chondrogenic markers SOX9 and ACAN also followed a robust sinusoidal rhythmic expression pattern. These rhythmic conditions significantly enhanced cartilage matrix production and upregulated marker gene expression. The observed chondrogenesis-promoting effect of the mechanical environment was at least partially attributable to its entraining effect on the molecular clockwork, as co-application of the small molecule clock modulator longdaysin attenuated the stimulatory effects of mechanical load. This study suggests that an optimal biomechanical environment enhances tissue homoeostasis and histogenesis during chondrogenesis at least partially through entraining the molecular clockwork.

show abstract

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 77%

Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock

Vágó

Katona

Takács

et al. 2022

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…The circadian clock has been shown to play a key regulatory role in various tissues and organs, including the musculoskeletal system, and more specifically cartilage 15,45 . Our results, for the first time, suggest that entraining chondroprogenitor clocks during chondrogenesis by uniaxial cyclic mechanical load offers a novel and insightful way in which these cells can be primed to produce more abundant cartilage ECM.…”

Section: Discussionmentioning

confidence: 99%

Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock

Vágó

Katona

Takács

et al. 2021

Preprint

View full text Add to dashboard Cite

Objective: The biomechanical environment plays a key role in regulating cartilage formation, but current understanding of mechanotransduction pathways in chondrogenic cells is still incomplete. Amongst the combination of external factors that control chondrogenesis are temporal cues that are governed by the cell-autonomous circadian clock. However, mechanical stimulation has not yet directly been proven to modulate chondrogenesis via entraining the circadian clock in chondroprogenitor cells. Design: The purpose of this study was to establish whether mechanical stimuli entrain the core clock in chondrogenic cells, and whether augmented chondrogenesis caused by mechanical loading was at least partially mediated by the synchronised, rhythmic expression of the core circadian clock genes, chondrogenic transcription factors, and cartilage matrix constituents. Results: We report here, for the first time, that cyclic uniaxial mechanical load applied for 1 hour for a period of 6 days entrains the molecular clockwork in chondroprogenitor cells during chondrogenesis in limb bud-derived micromass cultures. In addition to the several core clock genes, the chondrogenic markers SOX9, ACAN, and COL2A1 also followed a robust sinusoidal rhythmic expression pattern. These rhythmic conditions significantly enhanced cartilage matrix production and upregulated marker gene expression. The observed chondrogenesis-promoting effect of the mechanical environment was at least partially attributable to its entraining effect on the molecular clockwork, as co-application of the small molecule clock modulator longdaysin attenuated the stimulatory effects of mechanical load. Conclusions: Results from this study suggest that an optimal biomechanical environment enhances tissue homeostasis and histogenesis during early chondrogenesis through entraining the molecular clockwork.

show abstract

“…Its shape and biosynthetic properties remain invariable throughout its lifetime. 37 , 38 Inversely, condyle cartilage, as secondary cartilage, does not develop significantly until E15. Growth starts from mesenchymal tissue covering the prenatal or postnatal condyle, and it easily adapts to alterations in the environment.…”

Section: Cartilage and Bone Phenotypes Of Mouse Clock Gene Mutationsmentioning

confidence: 99%

“…The primary synovial joint articular cartilage grows from chondrocytes in the central layer of the epiphyseal plate, gradually differentiated from E11.5. Its shape and biosynthetic properties remain invariable throughout its lifetime 37,38 . Inversely, condyle cartilage, as secondary cartilage, does not develop significantly until E15.…”

Section: Cartilage and Bone Phenotypes Of Mouse Clock Gene Mutationsmentioning

confidence: 99%

Drivers of phenotypic variation in cartilage: Circadian clock genes

Song

Bai

Meng

et al. 2021

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Endogenous homeostasis and peripheral tissue metabolism are disrupted by irregular fluctuations in activation, movement, feeding and temperature, which can accelerate negative biological processes and lead to immune reactions, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This review summarizes abnormal phenotypes in articular joint components such as cartilage, bone and the synovium, attributed to the deletion or overexpression of clock genes in cartilage or chondrocytes. Understanding the functional mechanisms of different genes, the differentiation of mouse phenotypes and the prevention of joint ageing and disease will facilitate future research.

show abstract

Prospects of circadian clock in joint cartilage development

Cited by 3 publications

References 205 publications

Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock

Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock

Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock

Drivers of phenotypic variation in cartilage: Circadian clock genes

Contact Info

Product

Resources

About