Biology subjects

Bonassar, L.

Publications and source records attributed to Bonassar, L..

3 recordsLinked to original sources

bioRxiv2026

Cartilage canals in sharks and rays show that blood vessels can exist in mature cartilage without triggering endochondral bone formation

Although cartilage in tetrapod skeletons is typically said to lack blood vessels, this is only true for adult cartilage. In young bird and mammal cartilage, a dense network of vasculature-containing tunnels --cartilage canals-- perforate the growing skeleton, helping nourish the cartilage and develop the ossification centers that will later form the skeletons epiphyseal bone. As the canals and their rich vascular network typically recede as animals age, the healthy cartilage of adult animals is typically known to be avascular. Here, however, we use a range of tissue characterization and visualization techniques --including light/electron microscopy and microCT-- to show that the skeletons of rays and sharks (elasmobranch fishes) not only possess cartilage canals, but that these structures persist in the adult skeleton. The morphology and tissue composition of elasmobranch cartilage canals argues homology with mammalian cartilage canals and an ancient invasion of the vascular system into cartilage. However, the anatomical location of canals --extending away from mineralized tissue not toward it-- and the lack of endochondral ossification in ray and shark cartilage suggest that cartilage canals developed early in vertebrates as a transport system for nutrients and mesenchymal cells into the growing skeleton. We describe distinctive features and variation in elasmobranch cartilage canals, discuss their possible roles and their potential for tissue mineralization, and the biomedical implications for their presence in a clade of animals with continuously growing cartilaginous skeletons.

evolutionary biology↗

bioRxiv2024

Recombinant manufacturing of multispecies biolubricants

Lubricin, a lubricating glycoprotein abundant in synovial fluid, forms a low-friction brush polymer interface in tissues exposed to sliding motion including joints, tendon sheaths, and the surface of the eye. Despite its therapeutic potential in diseases such as osteoarthritis and dry eye disease, there are few sources available. Through rational design, we developed a series of recombinant lubricin analogs that utilize the species-specific tissue-binding domains at the N- and C-termini to increase biocompatibility while replacing the central mucin domain with an engineered variant that retains the lubricating properties of native lubricin. In this study, we demonstrate the tissue binding capacity of our engineered lubricin product and its retention in the joint space of rats. Next, we present a new bioprocess chain that utilizes a human-derived cell line to produce O-glycosylation consistent with that of native lubricin and a purification strategy that capitalizes on the positively charged, hydrophobic N- and C-terminal domains. The bioprocess chain is demonstrated at 10 L scale in industry-standard equipment utilizing commonly available ion exchange, hydrophobic interaction and size exclusion chromatography resins. Finally, we confirmed the purity and lubricating properties of the recombinant biolubricant. The biomolecular engineering and bioprocessing strategies presented here are an effective means of lubricin production and could have broad applications to the study of mucins in general.

bioengineering↗

bioRxiv2022

Mesenchymal Stromal Cells Donate Mitochondria to Articular Chondrocytes Exposed to Mitochondrial, Environmental, and Mechanical Stress

Avascular soft tissues of the skeletal system, including articular cartilage, have limited healing capacity, in part due to their low metabolic activity. No drugs are available that can prevent or slow the development of osteoarthritis (OA) after joint injury. Therefore, mesenchymal stromal cell (MSC)-based regenerative therapies are increasingly common in the treatment of OA, but questions regarding their clinical efficacy and mechanisms of action remain unanswered. Our group recently reported that mitochondrial dysfunction is one of the earliest responses of cartilage to injury, resulting in chondrocyte death, extracellular matrix degeneration, and ultimately OA. MSCs have been found to rescue injured cells and improve healing by donating healthy mitochondria in highly metabolic tissues, but mitochondrial transfer has not been investigated in cartilage. Here, we demonstrate that MSCs transfer mitochondria to stressed chondrocytes in cell culture and in injured cartilage tissue. Conditions known induce chondrocyte mitochondrial dysfunction, including stimulation with rotenone/antimycin and hyperoxia, increased transfer. Stressed chondrocytes increased expression of genes related to inflammation and senescence, further supporting the link between mitochondrial dysfunction and transfer. MSC-chondrocyte mitochondrial transfer was blocked by non-specific and specific (connexin-43) gap-junction inhibition. When MSCs were exposed to mechanically injured cartilage they localized to areas of matrix damage and extended cellular processes deep into microcracks, delivering mitochondria to chondrocytes. This work provides insights into the chemical, environmental, and mechanical conditions that can elicit MSC-chondrocyte mitochondrial transfer in vitro and in situ, and our findings suggest a new potential role for MSC-based therapeutics after cartilage injury. Significance StatementRecent evidence suggests that although articular cartilage is avascular and relatively metabolically quiescent, acute injury induces chondrocyte mitochondrial dysfunction, driving cartilage degradation and OA. We present the first evidence that MSCs donate mitochondria to articular chondrocytes undergoing mitochondrial dysfunction in vitro and in situ. These findings support a new role for MSCs in the context of cartilage injury and OA, and intercellular mitochondrial transfer may represent a new biological approach to augment mitochondrial capacity in injured chondrocytes. This work establishes multiple experimental models to study MSC mitochondrial donation for the treatment of OA and related degenerative diseases of avascular orthopedic tissues.

cell biology↗