Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in the medial compartment of OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. As a step toward evaluating the causality of PLR suppression in OA, we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact, using Cre recombinase driven by the 9.6-kb DMP1 promoter. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, defects in PLR coincide with cartilage defects. Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis, likely via its effects on PLR. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis.

Rotator cuff disease encompasses a broad spectrum of injury and pathology with an increasing incidence with age. Pain with overhead activity, localizing to the deltoid region, and loss of active range of motion of the shoulder are among the most common presenting symptoms. Treatment options are dependent on the extent of disease and patient symptoms, and may range from physical therapy to surgical repair using a variety of possible techniques. Tear thickness, size, and morphology frequently dictate the repair techniques that are used, such as margin convergence, anterior and posterior interval slides, and mobilization of the rotator interval and supraspinatus with a subscapularis repair. Establishing and maintaining a low-tension repair is important in optimizing tendon healing after surgery. Superior capsule reconstruction is an emerging treatment strategy for massive, otherwise irreparable cuff tears, though more long-term evidence is necessary to fully evaluate this option.

Mesenchymal stem cells likely play a key role in healing following surgical procedures such as microfracture and ligament reconstruction. If local anesthetics are used following joint surgery, selection of an agent with low toxicity toward mesenchymal stem cells, such as ropivacaine, may maximize tissue healing potential.