Independent and combined effects of obesity and traumatic joint injury to the structure and composition of rat knee cartilage

ABSTRACT

Osteoarthritis (OA) is a multifactorial joint disease characterized by articular cartilage degradation. Risk factors for OA include joint trauma, obesity, and inflammation, each of which can affect joint health independently, but their interaction and the associated consequences of such interaction were largely unexplored. Here, we studied compositional and structural alterations in knee joint cartilages of Sprague-Dawley rats exposed to two OA risk factors: joint injury and diet-induced obesity. Joint injury was imposed by surgical transection of anterior cruciate ligaments (ACLx), and obesity was induced by a high fat/high sucrose diet. Depth-dependent proteoglycan (PG) content and collagen structural network of cartilage were measured from histological sections collected previously in Collins et al.. (2015). We found that ACLx primarily affected the superficial cartilages. Compositionally, ACLx led to reduced PG content in lean animals, but increased PG content in obese rats. Structurally, ACLx caused disorganization of collagenous network in both lean and obese animals through increased collagen orientation in the superficial tissues and a change in the degree of fibrous alignment. However, the cartilage degradation attributed to joint injury and obesity was not necessarily additive when the two risk factors were present simultaneously, particularly for PG content and collagen orientation in the superficial tissues. Interestingly, sham surgeries caused a through-thickness disorganization of collagen network in lean and obese animals. We conclude that the interactions of multiple OA risk factors are complex and their combined effects cannot be understood by superposition principle. Further research is required to elucidate the interactive mechanism between OA subtypes.

KEYWORDS:

• Osteoarthritis
• proteoglycans
• collagen structure
• densitometry
• polarized light microscopy

Acknowledgments

This study was supported by the Research Council of Finland [grant no. 324529, 354916], Alberta Innovates – Health Solutions, the Canadian Institute Institutes of Health Research, Canadian Network for Research and Innovation in Machining Technology, the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canada Research Chair Program, the Killam Trusts, Kuopio University Foundations, Magnus Ehrnrooth Foundation, Maire Lisko Foundation, Marie Skłodowska-Curie Actions postdoctoral fellowship [grant no. 890936], the Carleton University internal start-up research fund [186725], the NSERC Discovery grant [funding reference no: DGECR-2023-00346], the Nigg Chair for Biomechanics Research, Päivikki and Sakari Sohlberg Foundation, Sigrid Juselius Foundation and Strategic Funding of the University of Eastern Finland. Novo Nordisk foundation (grant no. NNF21OC0065373). We would like to thank Dr Santtu Mikkonen, Ph.D., from University of Eastern Finland for providing his expertise with statistics for our analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/03008207.2024.2310838.

Additional information

Funding

This work was supported by the Academy of Finland [grant no. 324529]; NSERC Discovery grant [funding reference no: DGECR-2023-00346]; Carleton University internal start-up research fund [186725]; Canadian Institute Institutes of Health Research, Canadian Network for Research and Innovation in Machining Technology [NA]; Killam Trusts, Kuopio University Foundations, Magnus Ehrnrooth Foundation, Maire Lisko Foundation, Marie Skłodowska-Curie Actions postdoctoral fellowship [grant no. 890936].