Once believed to be limited to articular cartilage, osteoarthritis is now considered to be an organ disease of the “whole joint.” Damage to the articular surface can lead to, be caused by, or occur in parallel with, damage to other tissues in the joint. The relationship between cartilage and the underlying subchondral bone has particular importance when assessing joint health and determining treatment strategies. The articular cartilage is anchored to the subchondral bone through an interface of calcified cartilage, which as a whole makes up the osteochondral unit. This unit functions primarily by transferring load-bearing weight over the joint to allow for normal joint articulation and movement. Unfortunately, irreversible damage and degeneration of the osteochondral unit can severely limit joint function. Our understanding of joint pain, the primary complaint of patients, is poorly understood and past efforts toward structural cartilage restoration have often not been associated with a reduction in pain. Continued research focusing on the contribution of subchondral bone and restoration of the entire osteochondral unit are therefore needed, with the hope that this will lead to curative, and not merely palliative, treatment options. The purpose of this narrative review is to investigate the role of the osteochondral unit in joint health and disease. Topics of discussion include the crosstalk between cartilage and bone, the efficacy of diagnostic procedures, the origins of joint pain, current and emerging treatment paradigms, and suitable preclinical animal models for safety and efficacy assessment of novel osteochondral therapies. The goal of the review is to facilitate an appreciation of the important role played by the subchondral bone in joint pain and why the osteochondral unit as a whole should be considered in many cases of joint restoration strategies. Impact Statement In this comprehensive review, we are providing a holistic overview of osteochondral tissue development, disease, pain localization, as well as structural evaluation and current repair strategies. This review is intended to serve as a broad introduction to this multidisciplinary research area. It is a thorough examination of the biological aspects of the osteochondral unit from a tissue engineering perspective, highlighting the importance of the subchondral bone in chondral and osteochondral lesion repair and pain relief.

Background Delta-9-tetrahydrocannabinol (THC) is the primary phytocannabinoid responsible for the psychoactive properties of cannabis and is known to interact with the endocannabinoid system, which is functionally present in the male reproductive system. Since cannabis consumption is the highest among reproductive aged males, the current study aimed to further investigate the effects of THC exposure to phenotypical, physiological, and molecular parameters in sperm. Bull sperm of known fertility were used as a translational model for human sperm and subjected to in vitro treatment with physiologically relevant experimental doses of THC. Sperm parameters, capacitation, apoptosis, and transcript levels were evaluated following treatment. Results Motility, morphology, and viability of bovine sperm was unaltered from THC exposure. However, 0.32µM of THC caused an increased proportion of capacitating sperm (p < 0.05) compared to control and vehicle group sperm. Transcriptome analysis revealed that 39 genes were found to be differentially expressed by 0.032µM THC exposure, 196 genes were differentially expressed by 0.32µM THC exposure, and 33 genes were differentially expressed by 3.2µM THC. Secondary analysis reveals pathways involving development, nucleosomes, ribosomes and translation, and cellular metabolism to be significantly enriched. Conclusion Phytocannabinoid exposure to sperm may adversely affect sperm function by stimulating premature capacitation. These findings also show for the first time that spermatozoal transcripts may be altered by THC exposure. These results add to previous research demonstrating the molecular effects of cannabinoids on sperm and warrant further research into the effects of cannabis on male fertility.

Bisphenol A (BPA) and its analogs, bisphenol S (BPS) and bisphenol F (BPF), might impact fertility by altering oxidative stress pathways. Here, we hypothesize that bisphenols-induced oxidative stress is responsible for decreased gamete quality. In both female (cumulus-oocyte-complexes—COCs) and male (spermatozoa), oxidative stress was measured by CM-H2DCFDA assay and key ROS scavengers (SOD1, SOD2, GPX1, GPX4, CAT) were quantified at the mRNA and protein levels using qPCR and Western blot (COCs)/immunofluorescence (sperm). Either gamete was treated in five groups: control, vehicle, and 0.05 mg/mL of BPA, BPS, or BPF. Our results show elevated ROS in BPA-treated COCs but decreased production in BPS- and BPF-treated spermatozoa. Additionally, both mRNA and protein expression of SOD2, GPX1, and GPX4 were decreased in BPA-treated COCs (p < 0.05). In sperm, motility (p < 0.03), but not morphology, was significantly altered by bisphenols. SOD1 mRNA expression was significantly increased, while GPX4 was significantly reduced. These results support BPA’s ability to alter oxidative stress in oocytes and, to a lesser extent, in sperm. However, BPS and BPF likely act through different mechanisms.

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