Research Interests

Dr. Maerz’s primary research area is the pathogenesis of post-traumatic osteoarthritis (PTOA) following joint injury, with a specific focus on the synovium and injury-induced molecular mechanisms that modulate the onset of joint degeneration. The Maerz laboratory has a strong translational focus, and each major research platform aims to discover druggable targets to develop novel, disease-modifying treatments for PTOA.

Given the expanding incidence of joint injury and the rapidly-growing burden of osteoarthritis and its associated musculoskeletal and non-musculoskeletal comorbidities, a critical need exists to alter the natural history of tissue degeneration following joint injury. Given the complex phenotype of PTOA, the Maerz lab employs multi-faceted assessments to discern in vivo molecular processes, gene and protein expression and content, pain sensitization, pathologic tissue remodeling, and cellular composition. A strong focus is placed on quantitative assessments of PTOA disease severity to minimize or eliminate subjective, qualitative evaluations, and quantitative imaging is used heavily to augment histological and molecular read-outs.

Current Projects 

Mapping the Synovial-Nerve Interactome

Osteoarthritis is associated with profound structural changes to many joint tissues, however ultimately joint pain is the primary clinical symptom which drives patients to seek care. The synovium has been previously implicated as a key source of joint pain in both early- and late-stage osteoarthritis. There is both preclinical and clinical data supporting the notions that new sprouting of pain-sensing nociceptive neurons occurs within the joint during osteoarthritis development and may contribute to increased synovial-derived pain, especially in early-stage osteoarthritis. Crosstalk between joint-innervating neurons and resident synovial cells, particularly synovial fibroblasts, has been implicated as a key facilitator of nociceptor sprouting, but the signaling mechanisms underlying this signaling are not well-understood. As part of the RE-JOIN consortium, our lab is applying a multi-‘omic approach, including bulk and single cell RNA sequencing as well as spatial transcriptomics, to characterize the synovium-nerve interactome in a preclinical model of post-traumatic osteoarthritis. Our goal is to uncover the key crosstalk pathways underpinning synovial-derived pain signaling during osteoarthritis development, toward the long term goal of uncovering novel therapeutic targets for mitigating synovial-derived pain in clinical osteoarthritis.

Conserved Pro-Fibrotic Fibroblast Signatures in Osteoarthritis and Systemic Sclerosis

Synovitis is characterized by immune cell infiltration and fibrosis, which are hallmarks of osteoarthritis (OA), and a primary clinical correlate to joint pain. Fibrosis in skin, lung, and other tissues is also a hallmark of systemic sclerosis (SSc). OA and SSc share many conserved pathomechanisms, including extracellular matrix changes and fibrosis, nociceptor sensitization, ectopic chondrogenesis and mineralization, and focal inflammatory infiltrates. This study utilizes publicly available human single cell RNA sequencing data to compare and contrast fibroblast cell states and gene expression patterns in OA and SSc tissues to elucidate conserved mechanisms underlying fibrosis in both conditions.

Integrative Lineage Tracing of ⍺SMA Synovial Fibroblasts

We have previously characterized multiple fibroblast subpopulations that emerge in the synovium after joint injury. One of these populations are ⍺SMA-expressing fibroblasts. We hypothesize that these ⍺SMA-expressing fibroblasts serve as a progenitor pool for emergent cell lineages that underpin key features of post-traumatic osteoarthritis (PTOA), including lining hyperplasia, fibrosis, and osteophyte formation. This study leverages both traditional genetic lineage tracing and single cell RNA sequencing in order to investigate the ⍺SMA lineage.

3D Imaging of Intra-Articular Fat via Contrast-Enhanced MicroCT

Post-traumatic osteoarthritis can be characterized by the fibrotic remodeling of articular fat. This project involves developing a methodology to identify and quantify articular fat in a 3D context as fibrosis progresses after an anterior cruciate ligament rupture has been induced.

The Role of Wnt Pathway Agonist R-spondin 2 in Post-traumatic Osteoarthritis

The Wnt pathway is integral to numerous developmental and homeostatic biological processes. R-spondins are a family of matricellular secreted proteins that function as Wnt agonists to facilitate Wnt signaling. Our close collaborator Dr. Kurt Hankenson, among others, has elucidated a role for R-spondin 2, an R-spondin family member, in the formation of bone. However, little is known about R-spondins in osteoarthritis, particularly following joint injury. Our preliminary data demonstrate that R-spondin 2 is highly induced in synovium from injured joints, and it secreted into the synovial fluid. This up-regulation of R-spondin 2 corresponds with the documented overactivation of Wnt signaling in osteoarthritis, given that R-spondin 2 promotes Wnt signaling. We are now pursuing the cell types in the joint that are responsible for secreting R-spondin 2, and studying the effects of R-spondin 2 on the diverse tissues that comprise the joint space, including synovium, cartilage, bone and fat. Our primary objectives through this work are to characterize the cellular and molecular mechanisms by which R-spondin 2 promotes joint degeneration following injury, and by leveraging our interest in biomaterial-mediated drug delivery, we aim to develop a sustained method of therapeutically targeting R-spondin 2 and Wnt signaling in post-traumatic osteoarthritis.

The Influence of Local and Systemic Stem Cells on Joint Inflammation and Catabolism

Exciting recent research points towards a stem cell component in the regulation of joint inflammation. Although it is recognized that mesenchymal stem/multipotent stromal cells (MSCs) possess anti-inflammatory and immunomodulatory capabilities, very little is known regarding their involvement in PTOA pathophysiology. The major objective of this research platform is to elucidate how both local and systemic MSCs can be leveraged to exert a therapeutic, inflammation-mitigating effect following joint trauma.

By studying intrinsic mechanisms responsible for regulating stem cell migration to injured joint tissues and their downstream modulation of the inflammatory response, the contribution of stem cells in thwarting the development of osteoarthritis can be defined. A specific chemotaxis-related signaling axis we are interested in is CXCL16-CXCR6 given the high endogenous CXCR6 expression on both mouse and human MSCs. Our laboratory has observed that CXCL16 is strongly upregulated by the synovium of injured knee joints, with fibroblast-like synoviocytes being a primary source. Ongoing loss-of-function and gain-of-function studies are understanding the impact of CXCL16-CXCR6 signaling on synovial MSC trafficking, synovitis, and overall PTOA severity.

Thrombospondin-2 and its Role in Pathological Angiogenesis following Joint Injury

Thrombospondins are a group of matricellular proteins regulating a wide variety of interactions in the mammalian skeleton. Thrombospondin-1 (TSP1) and -2 (TSP2) are endogenous anti-angiogenic proteins known to regulate blood vessel formation in various mesenchymal tissues, with a large body of research on their activity in bone published by a close collaborator of the Maerz lab, Dr. Kurt Hankenson. Our lab is focusing on Thrombospondin-2 (TSP2) and its regulation of the pathological angiogenesis that occurs following joint trauma, most notably in the synovium and at the osteochondral junction. Data from our lab show that the murine knee synovium strongly expresses TSP2 acutely after injury and out to timepoints of established PTOA. We view this upregulation as the joint’s native anti-angiogenic response, which is insufficient to combat the formation of new blood vessels that serve to perpetuate inflammation and catabolism. Intraarticular angiogenesis is also closely related to chondrocyte hypertrophy and ectopic endochondral ossification, which are known to occur in deep articular cartilage during the progression of OA and PTOA. The major objective of this research platform is to understand whether TSP2 can be therapeutically administered to injured joints to thwart intraarticular angiogenesis, thereby mitigating inflammation and tissue catabolism.

Endocannabinoid Signaling in PTOA-related Inflammation and Pain Sensitization

The endocannabinoid system (ECS) is a signaling system involved in both pain transmission and inflammation. Although pain and inflammation are highly relevant to PTOA and OA, a surprisingly small amount of research exists regarding the involvement of this signaling system in PTOA pathogenesis. While important work has been done to understand the analgesic and anti-inflammatory capacity of both endogenous and exogenous cannabinoids, we know very little about how cannabinoids and their receptors are regulated after joint injury and whether the ECS can be leveraged for therapeutic benefit. Ongoing and upcoming studies are elucidating how the ECS regulates the phenotype of the fibroblast- like synoviocyte (FLS), which is a primary effector cell orchestrating inflammation and tissue catabolism after joint injury. Given shifting societal and regulatory views on cannabis and cannabis-derived substances such as Cannabidiol (CBD), great and immediate translational potential exists on the use of cannabinoids to treat joint pain and inflammation. While systemic cannabinoid therapy is associated with significant off-target effects and given the relatively low bioavailability of systemically administered cannabinoids, we are working towards a local, intra-articular treatment. To this end, the major objective of this research platform is to develop a sustained, intra-articular therapy leveraging the anti-nociceptive and anti-inflammatory capacity of the ECS.