Modifying loading during gait leads to biochemical changes in serum cartilage oligomeric matrix protein concentrations in a subgroup of individuals with anterior cruciate ligament reconstruction.

Purpose: Strong observational evidence has linked changes in limb loading during walking following anterior cruciate ligament reconstruction (ACLR) to posttraumatic osteoarthritis (PTOA). It remains unknown if manipulating peak loading influences joint tissue biochemistry. Thus, the purpose of this study is to determine whether manipulating peak vertical ground reaction force (vGRF) during gait influences changes in serum cartilage oligomeric matrix protein (sCOMP) concentrations in ACLR participants.

CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis.

In osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain.

Sustained inhibition of CC-chemokine receptor-2 via intraarticular deposition of polymeric microplates in post-traumatic osteoarthritis.

Posttraumatic osteoarthritis (PTOA) is mostly treated via corticosteroid administration, and total joint arthroplasty continues to be the sole effective intervention in severe conditions. To assess the therapeutic potential of CCR2 targeting in PTOA, we used biodegradable microplates (µPLs) to achieve a slow and sustained intraarticular release of the CCR2 inhibitor RS504393 into injured knees and followed joint damage during disease progression. RS504393-loaded µPLs (RS-µPLs) were fabricated via a template-replica molding technique.

Early ablation of Ccr2 in aggrecan-expressing cells following knee injury ameliorates joint damage and pain during post-traumatic osteoarthritis.

Objective: To investigate whether Ccr2 inactivation in aggrecan-expressing cells induced before post-traumatic OA (PTOA) onset or during progression, improves joint structures, synovial thickness and pain.

Design: We induced a Ccr2 deletion in aggrecan-expressing cells (CCR2-AggKO) in skeletally mature mice using a tamoxifen-inducible Ccr2 inactivation. We stimulated PTOA changes (destabilization of medial meniscus, DMM) in CCR2-AggKO and CCR2+/+ mice, inducing recombination before DMM or 4 wks after DMM (early-vs late-inactivation).

CD73 Maintains Hepatocyte Metabolic Integrity and Mouse Liver Homeostasis in a Sex-Dependent Manner.

Background & Aims: Metabolic imbalance and inflammation are common features of chronic liver diseases. Molecular factors controlling these mechanisms represent potential therapeutic targets. CD73 is the major enzyme that dephosphorylates extracellular adenosine monophosphate (AMP) to form the anti-inflammatory adenosine.