Alkaptonuria (AKU) is characterised by increased circulating homogentisic acid and deposition of ochronotic pigment in collagen-rich connective tissues (ochronosis), stiffening the tissue. This process over many years leads to a painful and severe osteoarthropathy, particularly affecting the cartilage of the spine and large weight bearing joints. Evidence in human AKU tissue suggests that pigment binds to collagen. The exposed collagen hypothesis suggests that collagen is initially protected from ochronosis, and that ageing and mechanical loading causes loss of protective molecules, allowing pigment binding. Schmorl’s staining has previously demonstrated knee joint ochronosis in AKU mice. This study documents more comprehensively the anatomical distribution of ochronosis in two AKU mouse models (BALB/c Hgd^−/−, Hgd tm1a^−/−), using Schmorl’s staining. Progression of knee joint pigmentation with age in the two AKU mouse models was comparable. Within the knee, hip, shoulder, elbow and wrist joints, pigmentation was associated with chondrons of calcified cartilage. Pigmented chondrons were identified in calcified endplates of intervertebral discs and the calcified knee joint meniscus, suggesting that calcified tissues are more susceptible to pigmentation. There were significantly more pigmented chondrons in lumbar versus tail intervertebral disc endplates (p = 0.002) and clusters of pigmented chondrons were observed at the insertions of ligaments and tendons. These observations suggest that loading/strain may be associated with increased pigmentation but needs further experimental investigation. The calcified cartilage may be the first joint tissue to acquire matrix damage, most likely to collagen, through normal ageing and physiological loading, as it is the first to become susceptible to pigmentation.

Alkaptonuria (AKU) 的特征是循环尿黑酸增加和富含胶原的结缔组织中的黄褐斑沉积（黄褐斑），使组织变硬。多年的这个过程会导致疼痛和严重的骨关​​节病，特别是影响脊柱软骨和大的负重关节。人类 AKU 组织中的证据表明色素与胶原蛋白结合。暴露的胶原蛋白假说表明，胶原蛋白最初受到保护，不会出现黄褐斑，老化和机械负荷会导致保护性分子的损失，从而允许色素结合。Schmorl 染色先前已证明 AKU 小鼠的膝关节衰老。本研究更全面地记录了两种 AKU 小鼠模型（BALB/c Hgd ^-/-, Hgd tm1a ^-/- )，使用 Schmorl 染色。两种 AKU 小鼠模型中膝关节色素沉着随年龄的进展是可比的。在膝关节、髋关节、肩关节、肘关节和腕关节内，色素沉着与钙化软骨的软骨有关。在椎间盘钙化终板和钙化膝关节半月板中发现色素软骨，表明钙化组织更容易发生色素沉着。与尾部椎间盘终板相比，腰椎的色素软骨明显更多（p = 0.002) 并且在韧带和肌腱的插入处观察到色素软骨簇。这些观察结果表明，负荷/应变可能与色素沉着增加有关，但需要进一步的实验研究。钙化的软骨可能是第一个通过正常老化和生理负荷获得基质损伤的关节组织，最有可能是胶原蛋白，因为它是第一个对色素沉着敏感的关节组织。